UC San Diego

Dysbiosis of the gut microbiome, including elevated abundance of putative bacterial triggers,such as Escherichia coli (E. coli), is observed in inflammatory bowel disease (IBD). In this dissertation, we characterized the gut microbial community, one of its members - E. coli, and their implications in IBD. First, the evaluation of the entire gut microbial community of a cohort of IBD patients suggested that intestinal surgery has a significant impact on gut microbiome, including lowered diversity and stability, changes in bile acid levels and elevated E. coli abundance. This result calls for systematic evaluation of IBD treatment and careful consideration of treatment options. We then focused on E. coli through extracting de novo assemblies of dominant E. coli strains from time-series metagenomics data of an IBD patient. Analysis suggest that the E. coli community is highly dynamic with changing dominant strains, and certain strain-specific features may be correlated with pathogenicity and disease progression. Third, we characterized the metabolic functions of E. coli clinical isolates from IBD patients using comparative genomics analysis and genome-scale models. We identified metabolic genes that are specific to strains in B2 phylogroup that are more prevalent in IBD patients, which potentially enable colonization to human gut. Lastly, we evaluated the most updated transcription regulatory network (TRN) of E. coli, as it enables adaptation to various conditions including the inflamed digestive tract of IBD patients. We found that the TRN has robust core functional modules, and has significantly expanded in the past decade, but still has limited coverage, motivating more high-throughput experiments to ll in knowledge gaps. In conclusion, this dissertation broadened the understanding of E. coli and gut microbiome in IBD, and provided valuable insight for clinical practice and potential intervention strategies.