Maternal microbiome promotes offspring ovarian reserve via bile acid metabolism.

The maternal microbiome plays a crucial role in host ovarian function and fertility, yet its influence on in-utero ovarian development in offspring remains poorly understood. Here, we demonstrate that maternal antibiotic-induced microbiome disruption in mice leads to diminished ovarian reserve (DOR) in the offspring, while fecal microbiota transplantation (FMT) alleviates this effect. Metabolomic analysis reveals that maternal microbiome disruption alters metabolomic profiles in the maternal serum, with pathway enrichment analysis indicating reduced bile acid secretion in the maternal serum of ABX dams. Importantly, supplementation of key bile acid metabolites and transplantation of Lactobacillus gasseri (L. gasseri), a known promoter of bile acid metabolism, to antibiotic-treated dams abrogated maternal microbiome disruption-induced DOR. Additionally, through in vitro fertilization assay, we found that maternal microbiome disruption impaired oocyte quality in offspring, while FMT and supplementation with bile acid metabolites alleviated this effect. Together, our findings highlight the critical role of the maternal microbiome in offspring fertility, potentially through microbially mediated bile acid metabolism in the maternal serum.