Shaw, LP; (2018) The microbial ecology of human-associated bacterial communities. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The bacterial communities within the human body have important associations with health and disease. Understanding their complexity requires ecological approaches. In this thesis, I apply ecological techniques and models to explore the microbial ecology of human-associated bacterial communities at multiple scales. In the first half of this thesis, I explore the oral microbiome using 16S rRNA gene sequencing data to characterise the effect of various factors on its diversity. Multiple factors apart from disease can also affect the oral microbiome, but their relative importance remains a matter of debate. In Chapter 2, I use a dataset of saliva samples from a family of related Ashkenazi Jewish individuals to show that host genetics plays much less of a role than shared household in explaining bacterial community composition. In Chapter 3, I use a large dataset of plaque samples from women in Malawi to investigate associations between bacterial taxa and periodontal disease. I show that the signals from gingivitis and periodontitis can be distinguished, and use correlation networks to identify important taxa for the development of disease. The second half of this thesis deals with the effect of antibiotics on the human microbiome. I demonstrate new approaches at two extremes of scale: abstracting the gut microbiome to a single metric, and also investigating the worldwide distribution and diversity of a single resistance gene. In Chapter 4, I develop a new and simple mathematical model of the gut microbiome's response to antibiotic perturbation and fit it to empirical data, showing that in some individuals the gut microbiome appears to return to an alternative stable state, raising questions about the long-term impact of antibiotics on previously healthy bacterial communities. Antibiotic use also selects for resistance, which is a growing concern, particularly as resistance can be transmitted horizontally on mobile genetic elements. In Chapter 5, I describe a global dataset of isolates containing the mobilized colistin resistance gene mcr-1 and use the diversity present within a composite transposon alignment to explore its distribution and spread across multiple bacterial communities.

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