<b>Maternal gut microbiota programs stem cell functions in the offspring</b>

The maternal-microbiome influences child health. However, its impact on offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of maternal-microbiome in conditioning the offspring’s stem cells, we manipulated maternal-microbiota using Akkermansia muciniphila. Different maternal-microbiomes had distinct effects on proliferation and differentiation of stem cells in the offspring's gut and brain, influencing their developmental-trajectory and long-term health. Transplantation of altered maternal-microbiota into germ-free mice transmitted these stem cell-phenotypes to the recipients’ offspring. Progeny of germ-free mice selectively-colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal-microbiomes enriched the levels of circulating SCFAs and amino acids leaving distinct transcriptomic imprints on the mTOR-pathway of offspring’s stem cells. Blocking mTOR-signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of maternal-microbiome in programming offspring’s stem cells and represents a promising target for interventions.