Date of Award

Spring 2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Immunobiology

First Advisor

Palm, Noah

Abstract

The microbiota, comprising the trillions of microorganisms that colonize barrier tissues, exert profound effects on host health and disease. Microbial effects on host physiology have been illuminated by a wealth of sequencing-based approaches that enumerate bacterial species, strains, genes, and products (collectively, “multi-omics” approaches) at different tissue sites and in different human populations. Microbes may influence local physiology at their site of residence, as well as having systemic effects including perturbation of organism-wide metabolism, with wide-ranging consequences. The molecular mechanisms by which microbes mediate both local and systemic effects, however, remain mostly unclear. This is in part due to technological limitations in profiling microbes at the scales necessary to characterize the thousands of unique strains and species that comprise the collective human microbiota. The identification of specific host pathways engaged or modulated by particular microbes will provide insight into how the microbiota impacts host physiology, and suggest nodes of intervention for the amelioration of microbiota-mediated disorders. In this thesis, I will describe a new technological approach to profile direct microbial interactions with the host and how discoveries enabled by this technique may shape our future understanding of host-microbe interactions.

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