Perinatal ampicillin exposure alters murine maternal fecal bile acid and acylcarnitine profiles.
Maternal ampicillin exposure in mice alters the microbiome and metabolome, potentially impacting offspring weight gain. Human implications remain to be validated.
Where it sits
this study against the rest of the l-carnitine (levocarnitine) corpusSummary and findings
The study investigated the effects of maternal ampicillin exposure on the fecal microbiome and metabolome in a murine model. Significant microbial shifts and metabolic changes, including elevated fecal acylcarnitines, were observed. These changes were associated with increased weight gain in offspring.
Abstract
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 <i>in vivo</i> 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 <i>Muribaculaceae</i> family, including <i>Muribaculum intestinale</i> and <i>Duncaniella dubosii</i>, accompanied by a cohort-dependent enrichment of <i>Enterococcus</i> and <i>Prevotella</i> 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.
Background
The study addresses the impact of maternal antibiotic use on offspring development, focusing on the microbiome and metabolome changes. Antibiotic prophylaxis during and after childbirth is common, yet its long-term effects on offspring are not well understood. This research aims to elucidate the mechanisms by which maternal antibiotic exposure may influence early growth and immune development.
Methods
The study utilized a preclinical murine model to examine the effects of maternal ampicillin administration. The focus was on changes in the maternal fecal microbiome and metabolome, with specific attention to bacterial species and metabolic profiles. Primary outcomes included microbial composition and metabolic changes, particularly in bile acids and acylcarnitines.
Results
Ampicillin treatment led to significant depletion of Muribaculaceae family species and enrichment of Enterococcus and Prevotella species. Metabolic changes included elevated fecal acylcarnitines and altered bile acid profiles. Two new trihydroxylated bile acids were identified and synthesized. These changes were associated with increased weight gain in offspring.
Interpretation
The findings suggest that maternal antibiotic exposure can significantly alter the microbiome and metabolome, potentially affecting offspring development. While the results are statistically significant, their clinical relevance in humans remains uncertain due to the preclinical nature of the study. Further research is needed to confirm these effects in human populations.
Key findings
- Significant depletion of Muribaculaceae family species.
- Cohort-dependent enrichment of Enterococcus and Prevotella species.
- Elevated fecal acylcarnitines observed.
- Altered bile acid profiles with new trihydroxylated bile acids identified.
- Increased weight gain in offspring linked to maternal antibiotic exposure.
Limitations
- preclinical murine model
- no human data
- mechanistic insights only
- potential species-specific effects