/ en Tue, 02 Apr 24 11:00:00 -0400 /news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Tue, 02 Apr 2024 15:00:00 +0000 adicorat 5556761 at /news/study-reveals-links-between-blood-vessel-biology-and-heart-disease-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Wed, 07 Feb 2024 16:50:22 +0000 tulrich@broadinstitute.org 5556406 at /news/retinal-images-and-genetic-data-researchers-predict-cardiovascular-metabolic-and-other-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/657/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/657/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" 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field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Thu, 25 Jan 2024 15:31:37 +0000 tulrich@broadinstitute.org 5556336 at /news/new-patient-partnered-research-project-will-study-heart-disease-and-diabetes-risk-south-asian <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/657/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/657/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" 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field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Mon, 23 Oct 2023 14:19:37 +0000 Corie Lok 5555881 at /news/more-diverse-datasets-lead-better-genetic-risk-prediction-heart-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Thu, 06 Jul 2023 15:00:00 +0000 leah@broadinstitute.org 1282446 at /news/lipocyte-profiler-metabolic-biology-tool <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" 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<div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Fri, 30 Jun 2023 14:30:09 +0000 makenziekohler 1282386 at /news/artificial-intelligence-system-predicts-consequences-disruptions-genetic-networks <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Tue, 30 May 2023 18:00:41 +0000 tulrich@broadinstitute.org 1282331 at /blog/whyiscience-qa-machine-learning-engineer-builds-algorithms-improve-clinical-research <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Tue, 06 Dec 2022 18:47:34 +0000 adicorat 1242901 at /news/massive-international-study-uncovers-genes-involved-heart-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Tue, 06 Dec 2022 16:00:00 +0000 leah@broadinstitute.org 1276286 at /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" class="datetime">April 2, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists link certain gut bacteria to lower heart disease risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-04-02T11:00:00-04:00" title="Tuesday, April 2, 2024 - 11:00" class="datetime">April 2, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&itok=SXF26YYo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=TqIxC98a 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/oscillibacter_main.png?h=4693aea5&itok=i4nRa2vq 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&itok=2Wn2ZTz1 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/oscillibacter_main.png?h=4693aea5&itok=9_LoY7Ug" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Ahmed Mohamed </div> <div class="media-caption__description"> Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" 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<div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=PbyU4-6k 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=rwIhW76m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=Ib-lY3te 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Gut_microbes_heart_v2.png?h=d3e04ee7&itok=EXPQZtKF" alt="Susanna Hamilton, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cholesterol-busting gut bacteria may affect people’s cardiac health</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the ӳ����ý of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in <em><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Cell</a></em>, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.</p> <p>Members of <a href="/node/4721">Ramnik Xavier’s</a> lab, ӳ����ý’s <a href="/node/8539">Metabolomics Platform</a>, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called <em>Oscillibacter</em> take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.</p> <p>“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the ӳ����ý. He is also a professor at Harvard Medical School and Massachusetts General Hospital.</p> <p>Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.</p> <h2>Cholesterol cues</h2> <p>In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person's triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.</p> <p>In the new study, the ӳ����ý team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the <a href="https://www.framinghamheartstudy.org/fhs-about/" target="_blank">Framingham Heart Study</a>. </p> <p>“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”</p> <p>The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the <em>Oscillibacter</em> genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the <em>Oscillibacter</em> genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. </p> <p>The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included <em>Oscillibacter</em>. </p> <p>After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain <em>Oscillibacter</em> in the lab. </p> <p>The team found another gut bacterial species, <em>Eubacterium coprostanoligenes</em>, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30295-X" target="_blank">previously shown</a> is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with <em>Oscillibacter</em> on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.</p> <h2>Microbial messages</h2> <p>The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.</p> <p>“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”</p> <p>“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Li C, Stražar M, et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00305-2" target="_blank">Gut microbiome and metabolome profiling in Framingham Heart Study reveals cholesterol-metabolizing bacteria</a>. <em>Cell</em>. Online April 2, 2024. DOI:10.1016/j.cell.2024.03.014.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolomics-platform" hreflang="en">Metabolomics Platform</a></div> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/cardiovascular-disease" hreflang="en">Cardiovascular disease</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at