Date of Award

Fall 10-1-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Immunobiology

First Advisor

Palm, Noah

Abstract

Gut commensal microbes that elicit human immune responses are noteworthy for their ability to influence both local mucosal inflammation and, more rarely, systemic antibody responses. Here we isolated and characterized novel strains belonging to genus Allobaculum from inflammatory bowel disease (IBD) stool samples. In defined gnotobiotic mouse models we recapitulated the inflammatory effects of Allobaculum sps. and their notable induction of systemic immune responses at baseline. A microbial ecology screen revealed that this taxon is inversely correlated with Akkermansia muciniphila, and co-colonization experiments uncovered microbe-dependent redirection of immune phenotypes, which we term reciprocal epistasis. These immunostimulatory gut commensal strains exemplify the remarkable effects microbial ecology can have upon inflammation and immunity, as well as present a framework for unraveling the complexity of the gut microbiota with more mechanistic insight.

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