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Gut Bacteriophage Alterations after Fecal Microbiota Transplantation for Recurrent or Refractory Clostridioides difficile Infection

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Title: Gut Bacteriophage Alterations after Fecal Microbiota Transplantation for Recurrent or Refractory Clostridioides difficile Infection
Author: Niergarth, Jessmyn Adriane
Department: Department of Mathematics and Statistics
Program: Bioinformatics
Advisor: Feng, ZenyKim, Peter T.
Abstract: Clostridioides difficile infection (CDI) is a concern for health care providers around the world because CDI can be acquired nosocomially, and has high rates of treatment failure and recurrence (rCDI). Alternative therapeutic options have been explored, including fecal microbiota transplantation (FMT). FMT is a promising alternative to antibiotics that has been shown to achieve high cure rates for rCDI. Its mechanism of success is not fully understood and could potentially involve gut bacteriophages (phages), so we investigated the gut phage changes after FMT treatment of recurrent or refractory CDI. To achieve this objective, we purified DNA phages from fecal samples of rCDI patients treated with FMT, and from FMT donor samples. We created an in-house bioinformatics pipeline to preprocess raw metagenomic shotgun sequencing phage reads and identify phages from the fecal samples. We proposed a three-step statistical analysis procedure to analyze the association between HRQoL measures and phage abundances. We also explored the transition patterns of phage communities in patients from pre-FMT to post-FMT. We found that the Shannon diversity and proportion of reads mapping to donor phage contigs increased, and the Caudovirales:Microviridae ratio decreased in patients after FMT. These results suggest that donor phages were engrafted into or augmented in patients via FMT, and that these changes lead to a gut phageome more similar to that of a healthy individual. Our regularized mixed effects regression model for joint selection of dsDNA phages that were associated with Bodily Pain produced a final model that retained 36 phages as covariates. These phages are potential targets for future work and included five Leuconostoc phages, six Lactococcus phages, and one C. difficile phage. Leuconostoc and Lactococcus bacteria are associated with food, so our findings suggest that patient diet should be controlled for in future work. Within phages predicted to infect Proteobacteria, there was a relatively high abundance of phages predicted to infect Gammaproteobacteria, a bacterial class with a high proportion of pathogenic species. FMT donors were screened for pathogenic gut bacteria, but to further ensure the safety of FMTs, Gammaproteobacteria and their associated phages in FMTs could be studied further.
Date: 2020-09
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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Attribution-NonCommercial-NoDerivatives 4.0 International Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International