Maternal gut microbiota influence stem cell function in offspring

The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the 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 neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The 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 short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions. • Maternal gut microbiota shapes the stem cell characteristics of offspring • Maternal microbiota during pregnancy have lasting impacts on offspring physiology • Metabolites from maternal microbiota during pregnancy program offspring stem cells • The maternal microbiota-stem cell axis in offspring is driven by the mTOR pathway Dang et al. demonstrate that maternal gut microbiota during pregnancy program the intestinal and neuronal stem cell characteristics of offspring. This crosstalk between maternal microbiota and fetal stem cells, mediated by circulating metabolites, impacts offspring development, long-term health, behavior, and disease recovery.