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Abstract

The genomes of microorganisms that reside in and on the human body vastly outnumber human genes, implying that the human microbiome may be important for precision medicine. Humans have been canonically considered sterile in utero, with the majority of colonization occurring during, and immediately following, birth. Factors that have been shown to affect the ecology and succession of the microbiome include host genetic factors, maternal transmission, and environmental exposures. Furthermore, the timing of microbial exposure in relation to immune system development may have lifelong consequences. In this thesis, I investigated the early life microbiome through two lenses: that of microbiome assembly and that of human genotype. I first analyzed a longitudinal data set of preterm infants, who underwent abnormal and premature microbial exposure, characterized by delayed maturation and higher abundance of potential opportunistic pathogens. I identified associations between microbiome dynamics and infant growth outcomes during their first weeks of life, implying that there may be a link between the microbiota and preterm infant development. I also used human fucosyltransferase 2 (FUT2) genotype to probe the interplay between host genetics and the microbiome in a cross-sectional cohort of post-weaning toddlers. FUT2 secretor status plays an important role in formation of immune complexes, secretion of antigens in body fluid, and susceptibility to pathogenic bacteria. I found differences in microbial community composition and structure between children with different FUT2 genotypes. Bacteria from the same genera were differentially abundant in FUT2 secretors and FUT2 non-secretors, providing evidence for niche differentiation. As laid out in this thesis, both events surrounding birth and individualized human genotypes seem to associate with the microbiome in early life, indicating that these factors require consideration in future study.

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