Perinatal ampicillin exposure alters murine maternal fecal bile acid and acylcarnitine profiles

Maternal intrapartum antibiotic prophylaxis (IAP) and postpartum maternal antibiotic usage are increasingly common and have been linked to altered growth and immune development in offspring. However, the mechanisms underlying these effects, particularly those arising from indirect early-life exposure to antibiotics, remain poorly understood. Here, using a preclinical murine model, we examined the impact of in vivo antepartum and postpartum maternal ampicillin administration on the maternal fecal microbiome and metabolome. Ampicillin treatment resulted in a significant depletion of bacterial species belonging to the Muribaculaceae family, including Muribaculum intestinale and Duncaniella dubosii, accompanied by a cohort-dependent enrichment of Enterococcus and Prevotella species. These microbial shifts coincided with substantial and reproducible metabolic remodeling, including elevated fecal acylcarnitines and altered bile acid profiles. Notably, we identified two previously uncharacterized trihydroxylated bile acids conjugated to a hexose moiety, which we annotated as cholic acid-galactose and taurocholic acid-galactose and synthesized. These metabolites were consistently associated with antibiotic exposure across public metabolomics data repositories. Finally, alterations in the maternal fecal microbiome and metabolome were associated with increased weight gain in offspring, suggesting potential pathways by which maternal antibiotic exposure may influence early developmental outcomes. These findings highlight microbial and metabolic signatures linked to perinatal antibiotic use and underscore the need to balance infection control with long-term infant health considerations.