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Published on: January 27, 2019
Prenatal Maternal Antibiotics Treatment Alters the Gut Microbiota and Immune Function of Post-Weaned Prepubescent
Abdullah M Madany1,2, Heather K Hughes2,3, Paul Ashwood2,3
1Department of Psychiatry and Behavioral Sciences, University of California at Davis, 2230 Stockton Blvd., Sacramento, CA 95817, USA.
Insights
Maternal antibiotic exposure alters offspring gut microbiota composition and function post-weaning. These changes persist and impact the gut-immune-brain axis, affecting cytokine levels in offspring.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
- Developmental Biology
Background:
- Antibiotic use during pregnancy can impact the maternal gut microbiome.
- The gut microbiome plays a crucial role in host development and immune function.
- The gut-immune-brain axis is sensitive to microbial and immune signals.
Purpose of the Study:
- To investigate the effects of maternal antibiotic treatment on offspring gut microbiota post-weaning.
- To assess the impact of maternal antibiotics on the gut-immune-brain connection in offspring.
- To determine the temporal dynamics of these alterations in early life.
Main Methods:
- Pregnant C57BL/6J dams were treated with a broad-spectrum antibiotic cocktail or vancomycin alone.
- Offspring gut microbiota composition and metabolic pathways were analyzed using 16S rRNA sequencing.
- Cytokine profiles in offspring circulation and brain tissue were measured.
Main Results:
- Maternal antibiotic treatment significantly altered offspring gut microbiota diversity, composition, and predicted metabolic pathways post-weaning.
- The most pronounced differences were observed at 5 weeks compared to 4 weeks of age.
- Reduced levels of peripheral chemokines and brain inflammatory cytokines (IL-1α, IL-2) were noted in offspring.
Conclusions:
- Maternal antibiotic administration induces lasting alterations in the offspring gut microbiome.
- These microbial changes undergo continuous transformation during early development after weaning.
- Evidence suggests a link between maternal antibiotic exposure, gut dysbiosis, and altered immune signaling in offspring.
Abstract:
This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin 1 mg/mL, neomycin 1 mg/mL, and vancomycin 0.5 mg/mL, or vancomycin 0.5 mg/mL alone, administered ad-lib orally to dams via drinking water during gestation and stopped after delivery. We analyzed the gut microbiota of offspring, cytokine profiles in circulation, and the brain to determine if there was evidence of a gut-immune-brain connection. Computationally predicted metabolic pathways were calculated from 16s rRNA sequencing data. ABX treatment can negatively affect the gut microbiota, including reduced diversity, altered metabolic activity, and immune function. We show that the maternal ABX-treatment continues to alter the offspring's gut microbiota diversity, composition, and metabolic pathways after weaning, with the most significant differences evident in 5-week-olds as opposed to 4-week-olds. Lower levels of chemokines and inflammatory cytokines, such as interleukin (IL)-1α and IL-2, are also seen in the periphery and brains of offspring, respectively. In conclusion, this study shows maternal antibiotic administration alters gut microbiome profiles in offspring, which undergoes a continuous transformation, from week to week, at an early age after weaning.
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