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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Influence of perinatal ampicillin exposure on maternal fecal microbial and metabolic profiles
Simone Zuffa1,2, Sydney P Thomas1, Ipsita Mohanty1,2
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Insights
Maternal antibiotic exposure alters the gut microbiome and metabolism in mothers, potentially impacting offspring development. This study reveals changes in beneficial bacteria and bile acids, linked to increased offspring weight gain.
Area of Science:
- Microbiology
- Metabolomics
- Developmental Biology
Background:
- Antibiotic exposure in early life is linked to altered offspring growth and immunity.
- Mechanisms underlying these effects remain poorly understood.
- Maternal antibiotic use, including intrapartum antibiotic prophylaxis (IAP), is common.
Purpose of the Study:
- To investigate the effects of antepartum and postpartum ampicillin administration on maternal gut microbiome and metabolic profiles.
- To identify specific microbial and metabolic changes associated with maternal antibiotic exposure.
- To explore potential links between maternal changes and offspring development.
Main Methods:
- Administration of ampicillin to dams during antepartum and postpartum periods.
- Analysis of maternal fecal microbiome composition.
- Profiling of fecal metabolic content, including acylcarnitines and bile acids.
- Comparison with public metabolomics data.
Main Results:
- Ampicillin depleted beneficial Muribaculaceae bacteria (e.g., Muribaculum intestinale) and enriched Enterococcus and Prevotella species.
- Significant metabolic remodeling observed, including elevated fecal acylcarnitines and altered bile acid profiles.
- Identification of novel hexose-conjugated trihydroxylated bile acids associated with antibiotic exposure.
- Maternal antibiotic-induced changes coincided with increased offspring weight gain.
Conclusions:
- Maternal ampicillin exposure significantly alters the gut microbiome and metabolome.
- These maternal changes are associated with altered offspring weight gain, suggesting a role in developmental trajectories.
- Further research is needed to understand the long-term health implications for infants.
Abstract:
Indirect exposure to antibiotics during early life, via maternal intrapartum antibiotic prophylaxis (IAP) or postpartum maternal antibiotic usage, is increasingly common and has been epidemiologically linked to altered growth and immune developmental trajectories in offspring. Nevertheless, the underlying mechanisms remain poorly understood. Here, we explored the effects of antepartum and postpartum maternal ampicillin administration on the dams' fecal microbiome and metabolic profiles in vivo. Ampicillin caused a reproducible depletion of beneficial bacterial species belonging to the Muribaculaceae family, including Muribaculum intestinale and Duncaniella dubosii, and led to cohort-dependent enrichments of Enterococcus and Prevotella species. These microbial alterations were accompanied by substantial metabolic remodeling, characterized by elevated fecal acylcarnitines and dysregulation of the bile acids profile. Intriguingly, we identified two previously uncharacterized trihydroxylated bile acids conjugated to a hexose moiety, which appeared to be associated with antibiotic exposure across public metabolomics repositories. These alterations in the fecal maternal microbiome and metabolome coincided with increased weight gain in offspring, suggesting a possible role for maternal antibiotic exposure in shaping early developmental trajectories. Further studies are warranted to elucidate the long-term implications of these changes in infant health.

