Prenatal Maternal Antibiotics Treatment Alters the Gut Microbiota and Immune Function of Post-Weaned Prepubescent 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.