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Abstract

Human genotypes and their environment interact to produce selectable phenotypes. How microbes of the human gut microbiome interact with their host genotype to shape phenotype is not fully understood. Microbiota that inhabit the human body are environmentally acquired, yet many are passed intergenerationally between related family members, raising the possibility that they could act like genes. Here, I present three studies aimed at better understanding how certain gut microbiota contribute to host phenotypes. In a first study, I assessed mother to child transmission in understudied populations. I collected stool samples from 386 mother-infant pairs in Gabon and Vietnam, which are relatively under-studied for microbiome dynamics, and in Germany. Using metagenomic sequencing I characterized microbial strain diversity. I found that 25-50% of strains detected in mother-infant pairs were shared, and that strain-sharing between unrelated individuals was rare overall. These observations indicate that vertical transmission of microbes is widespread in human populations. Second, to test whether strains acquired during infancy persist into adulthood (similar to human genes), I collected stool from an adolescent previously surveyed for microbiome diversity as an infant. This dataset represents the longest follow-up to date for the persistence of strains seeded in infancy. I observed two strains that had persisted in the gut despite over 10 years passing, as well as 5 additional strains shared between the subject and his parents. Taken together, the results of these first two studies suggest that gut microbial strains persist throughout life and transmit between host-generations, dynamics more similar to those of the host’s own genome than of their environment. Third, I tested whether gut microbes could confer a phenotype (lactose tolerance) to individuals lacking the necessary genotypes (lactase persistence). I studied 784 women in Gabon, Vietnam and Germany for lactase persistence (genotype), lactose tolerance (phenotype), and characterized their gut microbiomes through metagenomic sequencing. Despite the genotype, I observed that 13% of participants were lactose tolerant by clinical criteria; I termed this novel phenotype microbially-acquired lactose tolerance (MALT). Those with MALT harbored microbiomes enriched for Bifidobacteria, a known lactose degrader. These results indicate that Bifidobacteria - which is passed intergenerationally - can confer a phenotype previously thought to be under only host genetic control. Taken together, my thesis work lends weight to the concept that specific microbes inhabiting the human gut have the potential to behave as epigenetic factors in evolution.