Interactions among intestinal commensal bacteria and their contributions to gut microbiome composition and gastrointestinal disease

The gut microbiome is a dynamic ecosystem where commensal bacteria interact, cooperate, and compete to colonize and persist in the human host. Altered composition of the gut microbiome and its interaction with the intestinal mucosa and immune system are associated with many human diseases. Our laboratory is interested in how interactions among diverse species of Bacteroidetes, one of the most prevalent groups of intestinal commensals, contribute to colonization and persistence. Two areas of ongoing investigation are 1) changes in complex carbohydrate utilization among Bacteroidetes triggered by contact with related species, and 2) interbacterial antagonism mediated by the type VI secretion system. We apply proteomics to detect interbacterial responses, and a combination of bacterial genetics, in vitro competitive growth experiments, and gnotobiotic animal models to investigate their contributions to microbiome composition. We elucidate molecular mechanisms of key interbacterial responses using bacterial genetics, biochemistry, and structural biology. Our laboratory is also interested in gut microbiome profiling as a diagnostic and predictive tool in gastrointestinal pathology. To this end, we are developing 16S rDNA sequencing to characterize the colonic mucosa-associated microbiome in patient formalin-fixed paraffin embedded (FFPE) tissue. This technology will enable microbiome profiling as part of the existing pathology workflow, with opportunities to examine diagnostic disease associations and prediction of response to therapies.

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Department/Program Affiliations:
Pathology