Dynamics of the human gut microbiota in very early life
Immediately after birth, newborn babies experience rapid colonisation by microorganisms from their mothers and the surrounding environment. Diseases in childhood and later in life are potentially mediated through perturbation of the infant gut microbiota colonisations. 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. In this thesis, I generated and analysed the largest datasets of shotgun metagenomes, isolate genomes and metagenome-assembled genomes of the neonatal gut microbiota to date. In the largest birth cohort study of its kind, I profiled the gut microbiomes of 771 UK healthy term infants and mothers through shotgun metagenomic sequencing 1,679 longitudinal faecal samples. Here I report that the mode of delivery is a significant factor that affects the composition of the gut microbiota throughout the neonatal period, and into infancy. This is evident by the disrupted transmission of maternal Bacteroides strains, and high-level colonisation by opportunistic pathogens associated with the hospital healthcare environments (including Enterococcus, Enterobacter and Klebsiella species), in babies delivered by caesarean section. Furthermore, I validated culture-independent detection of pathogen species by matched large-scale culturing, and whole-genome sequencing of over 800 bacterial strains cultured from these babies identified virulence factors and clinically relevant antimicrobial resistance in opportunistic pathogens that may predispose to opportunistic infections. These findings highlight the critical role of the local environment in establishing the gut microbiota in very early life, and identify colonisation with antimicrobial-resistance-containing opportunistic pathogens as a previously underappreciated risk factor in hospital births.
Human gut microbiota, Microbiome, Metagenomics
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