Early Life Antibiotics Alters the Development of the Gut Microbiota and Mucosal Immune T cell Populations

Antibiotic exposure during early life is associated with development of auto‐inflammatory diseases, including asthma, multiple sclerosis and Crohn’s disease, although the mechanism remains unclear. Exposure to antibiotics and the resultant changes in gut microbiota during early-life may lead to disruption of normal mucosal immune development, as this is strongly influenced by commensal microbes. We hypothesized that antibiotic disruption of the microbiota during early life would have a prolonged impact on both gut microbiota community structure and  T cell function within the intestinal tract,  resulting in defective immune tolerance to the commensal gut microbiota in a genetically susceptible host (NOD2^-/-), leading to increased susceptibility to colitis. Neonatal WT and NOD2^-/- littermates received amoxicillin [200mg/L] in the drinking water from birth to weaning. Fecal samples collected at weaning were analyzed by targeted quantitative PCR (qPCR) of 16S ribosomal DNA for microbiota composition. Neonatal amoxicillin treatment resulted in a significant reduction of Bifidobacterium and Lactobacillus in WT and NOD2^-/- littermates. Phenotypes of intraepithelial (IEL) and lamina propria lymphocyte (LPL) populations were not different in control-treated WT and NOD2^-/- littermates. However, antibiotic-treated NOD2^-/- littermates showed an enhanced IL-17 response. Together, this suggests that neonatal antibiotic perturbation of microbiota development alters NOD2 signalling in microbe-driven immune responses.