Environmental factors and the human gut microbiome

Abstract

There is increasing evidence that the composition of the human gut microbiome has a key role in health. Environmental factors predominate over the genetic in shaping the microbiome, yet while the potential factors contributing to the extensive inter-individual differences of microbiota are numerous, many have yet to be analysed. This thesis provides exploratory evidence of the relationship between wider environmental variables and microbiota composition and variance using the national TwinsUK cohort. The first part of this thesis provides a conceptual framework for the environmental factors potentially impacting the gut microbiota comprising four broad domains: hostintrinsic, host-lifestyle, passive and distal. Then, selecting key tractable variables from each conceptual domain, observational methods are used to analyse their association with microbiota composition characterised using 16s rRNA gene sequencing data from the TwinsUK cohort. Previous studies have focused on host-intrinsic (e.g. genetic, host health status) and host-lifestyle (e.g. diet, drugs) factors. Diet has emerged as a key environmental determinant, but the best method to capture the overall contribution of diet to variance in microbiota was not known. Therefore, in the second part of this thesis three dietary indices are compared, demonstrating that the ‘Healthy Eating Index’ captures the majority of variance attributable to diet. Next, the focus of the thesis is to provide examples of underexplored environmental factors, hypothesised to be associated with microbiota composition; distalenvironmental factors and passive-environmental factors. The models used to analyse each of these factors incorporated key covariates related to host intrinsic and host lifestyle factors. The passive environment captures inadvertently consumed factors that are products of the distal via host-lifestyle, such as food contaminants. The passive environment is explored via the composition of tap water, and results suggest, but are not conclusive of, an association with microbiota composition. Future study of passive environmental factors is therefore merited. Finally, the distal environment is examined. Distal-environmental factors are those associated with the wider geosocial and spatial environment of the host. Here, it is explored via socioeconomic status and the host’s habitat; both studies demonstrate these understudied factors to have significant associations with multiple measures of the microbiota. These findings raise the possibility that the microbiota mediate the effect of distal factors on host health. In summary, within this thesis a conceptual framework is used to explore understudied environmental associates of microbiota variance. Although not comprehensive, the examples studied provide evidence that distal and passive environmental factors merit future exploration. The results are of interest not only in furthering understanding of influencers of microbiota composition, but also in contributing to knowledge of how an individual’s spatial environment interacts with their health.

Date of Award	1 Nov 2019
Original language	English
Awarding Institution	King's College London
Supervisor	Claire Steves (Supervisor) & Tim Spector (Supervisor)