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Exploration of the Role Donor and Recipient Microbiome Community Structure Plays in the Efficacy of Fecal Microbiota Transplant to Treat Ulcerative Colitis.
- CHAVIRA, ARIES
- Advisor(s): Knight, Rob
Abstract
Ulcerative colitis (UC) is a chronic autoimmune disorder of the gut affecting over one million Americans. The precise etiology is unknown; however, it commonly exhibits a loss of beneficial gut microbes that produce butyrate and short-chain fatty acids. Fecal Microbiota Transplant (FMT) is a promising therapeutic thought to restore UC gut dysbiosis. However, many questions remain regarding why FMT’s work for some individuals but not for others. To decrease this gap, we conducted a quantitative meta-analysis to explore the role patient, and donor microbiomes play in the efficacy of FMT to treat UC. Twenty-eight studies met the preliminary exclusion criteria, five of which were included in this analysis. We found that patients who experience a clinical response have a higher species richness prior to FMT than those who do not. All patients experience an increase in alpha diversity after FMT and a shift in beta diversity to their donors, irrespective of their clinical outcome. We generated a microbial log-ratio model capable of predicting a patient’s response to FMT with an area under the receiver operating characteristic (AUROC) of 0.73. Differential abundance testing confirmed the increase in known butyrate producers of the genus, Blautia, Ruminococcus, and Alistipes, in donors and responder, compared to non-responders that were also predictors of clinical response in the sparse log-ratio model. These results signify that non-responders may harbor microbial communities too sparse in beneficial microbes that may not be fully restored post-FMT treatment, compared to those who experience a clinical response.
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