A global microbiome axis underlying susceptibility to immune-mediated diseases
Harvard Medical School
Abstract:
Immune-mediated inflammatory diseases (IMIDs) exhibit striking geographic disparities, yet the microbial basis of these patterns remains unresolved. Here, we assemble a global atlas of the healthy microbiome, spanning 43 countries and representing over half of the world’s population. By integrating microbiome variation with global epidemiology data, we identify a conserved microbial signature, the ‘pathobiontaxis’, that predicts IMID burden across populations. Strikingly, this axis is driven by taxa associated with inflammation, yet is paradoxically enriched in healthy populations with the lowest disease burdens. We demonstrate that healthy carriers exhibit amplified TNF responses upon immune stimulation, consistent with trained immunity. Finally, leveraging migration as a natural experiment, we show that this axis is rapidly lost within South Asians immigrating to the United States, mirroring heightened disease susceptibility. These findings reveal inflammation-associated taxa as potential contributors to trained immunity and establish the healthy microbiome as a mechanistic lens into global disease
disparities.
Biography:
Ohad is a Rothschild and EMBO postdoctoral researcher in the Smillie lab at Massachusetts General Hospital, Harvard Medical School and the Ó³»´«Ã½. His research focuses on how gut bacteria adapt to inflammatory environments, combining large-scale human microbiome data with computational and evolutionary approaches. He develops methods to link bacterial variation - spanning species composition, strain-level diversity, and single-nucleotide polymorphisms - to host disease, with the goal of identifying causal mechanisms.