The human gastrointestinal tract is colonized by a diverse community of symbiotic microorganisms, mainly bacteria, that are known to play essential roles in maintaining the health of their human host. Disruption of this bacterial community has been associated with numerous diseases, including Colorectal Cancer (CRC). CRC is one of the leading causes of cancer-related deaths worldwide. As such, focus has been placed on the modulation of the bacterial community within the cancer-associated gut microbiome as the next step in possible CRC treatment and prevention strategies. To use the bacterial community for these purposes, a better understanding of the associations that exist between bacteria within the healthy human gut microbiome and how these associations have changed within the CRC-associated gut microbiome is direly needed. In this dissertation, we first utilized whole-genome shotgun sequence data from four previously published healthy human cohorts to explore the composition and community structure of the healthy gut microbiome across populations. We show that despite species carriage differences, bacterial communities across healthy human populations are similar in both their structure and functional capacities. In addition, we found that positive associations occur between taxonomically and functionally related species in the gut microbiome. In follow-up work, we employed a similar approach to study the bacterial community composition and structure in late-stage CRC patient gut microbiomes. We found key differences between CRC and healthy gut bacterial communities, suggesting an overgrowth of potentially pathogenic species classified as oral microbes. Additionally, a striking difference in the bacterial community structure was found which we believe to be a bacterial response to probable ecosystem changes associated with tumor formation in the CRC-associated gut microbiome. Overall, our findings shed new light on how the bacterial community is structured within the healthy gut microbiome and how this structure has changed in the late-stage CRC-associated gut microbiome.
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Doctor of Philosophy (Ph.D.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
College of Medicine
Loftus, Mark, "Bacterial Association Networks from Healthy and Cancer-associated Gut Microbiomes" (2021). Electronic Theses and Dissertations, 2020-. 726.