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BACKGROUND: Autophagy-related processes are crucial for maintaining cellular homeostasis in eukaryotic organisms. While alterations of these processes have been strongly linked to specific human disorders, including inflammatory bowel disease, neurodegenerative diseases, and metabolic syndromes, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms. Several studies indicate that gut microbiota or derived metabolites can modulate host autophagy at the gut mucosa level but also in peripheral organs. Here, we investigated in vitro and in vivo the potential of bacterial species commonly used in food fermentation (ferments) or for their health benefits (probiotics) to modulate host autophagy.METHODS: We screened 11 bacterial strains (lactobacilli and bifidobacteria) in vitro for autophagy induction in human epithelial cells. The most effective strain identified in vitro was then tested in vivo through long-term dietary supplementation in mice to confirm its pro-autophagic effects in the gut and a distant organ, the retina.RESULTS: In vitro screening of the 11 bacterial strains revealed a strain-dependent ability of bacteria to stimulate autophagy in human epithelial cells. The Lactobacillus helveticus strain VEL12193, isolated from cheese, emerged as the strongest autophagy inducer. Long-term dietary supplementation of mice with L. helveticus VEL12193 confirmed the pro-autophagic potential of this strain, as evidenced by autophagy stimulation in the gut mucosa but also at distance, in the retina. Finally, we identified membrane vesicles (MVs) from L. helveticus as a component involved in bacteria-induced autophagy in epithelial and immune cells, with lactate and specific lipid species potentially contributing to this effect.CONCLUSION: In this study, we present evidence that intervention with ferments/probiotics stimulates autophagy in multiple cell types and organs, and we show in vitro that MVs mediate this effect. Additionally, we identify L. helveticus VEL12193 as a promising candidate for the development of healthy-aging strategies.