Stunted microbiota and opportunistic pathogen colonisation in caesarean section birth

Immediately after birth, newborn babies experience rapid colonisation by microorganisms from their mothers and the surrounding environment(1). Diseases in childhood and later in life are potentially mediated through perturbation of the infant gut microbiota colonisations(2). However, the impact of modern clinical practices, such as caesarean section delivery and antibiotic usage, on the earliest stages of gut microbiota acquisition and development during the neonatal period (≤1 month) remains controversial(3,4). Here we report disrupted maternal transmission of Bacteroides strains and high-level colonisation by healthcare-associated opportunistic pathogens, including Enterococcus, Enterobacter and Klebsiella species, in babies delivered by caesarean section (C-section), and to a lesser extent, in those delivered vaginally with maternal antibiotic prophylaxis or not breastfed during the neonatal period. Applying longitudinal sampling and whole-genome shotgun metagenomic analysis on 1,679 gut microbiotas of 771 full term, UK-hospital born babies and mothers, we demonstrate that the mode of delivery is a significant factor impacting gut microbiota composition during the neonatal period that persists into infancy (1 month - 1 year). Matched large-scale culturing and whole-genome sequencing (WGS) of over 800 bacterial strains cultured from these babies identified virulence factors and clinically relevant antimicrobial resistance (AMR) in opportunistic pathogens that may predispose to opportunistic infections. Our findings highlight the critical early roles of the local environment (i.e. mother and hospital) in establishing the gut microbiota in very early life, and identifies colonisation with AMR carrying, healthcare-associated opportunistic pathogens as a previously unappreciated risk factor.