The gut microbiome as a modifiable risk factor in recurring communicable and chronic non-communicable intestinal diseases
The dissertation aimed to evaluate the gut microbiome as a novel and versatile tool, both as a diagnostic biomarker for colorectal cancer (CRC) which is a long term chronic disease, as well as an intervention in the form of fecal microbial transplantation (FMT) for recurring Clostridium difficile infection (CDI). CRC is a leading cause of cancer-associated mortality in the United States and survival is vastly improved with early diagnosis. Fecal occult blood test (FOBT), the current non-invasive test for CRC has limited sensitivity (single test 60%-85%) and reasonable specificity. Improving the predictive value of the diagnostic test by detecting microbial markers in feces offers a promising screening option especially if the changes in the microbiome composition can reflect early stage disease. Re- analyzing raw molecular data through a sequence-based meta-analysis of CRC- fecal and mucosal microbiome studies, this dissertation aimed to determine a fecal biomarker for the disease, compare the fecal and mucosal microbiome composition in cases, and compare the mucosal microbiome in cancer tissue with pathologically healthy tumor adjacent tissue obtained from the same case. In the meta-analysis of fecal microbiome – CRC association studies several strains including Parvimonas micra ATCC 33270, Streptococcus anginosus and yet-to-be-cultured members of Proteobacteria, were frequently and significantly increased in stools from CRC patients compared to controls across. Combining clinical features such as FOBT and microbial features improved the diagnostic accuracy of detecting CRC. From the biopsy microbiome meta-analysis, we corroborated the dominance of Fusobacterium sp. in tumor biopsies as compared to tumor adjacent mucosa and observed a trend for Parvimonas sp. and Bacteroides fragilis to be consistently elevated in tumor biopsy as well as be measured well in stool. Investigating the utility of the microbiome in infectious diseases, the dissertation aimed to determine the temporal changes in microbiota introduced by FMT administered to the colon of an infected person in various fecal forms (fresh vs. frozen vs lyophilized) in subjects with multiply recurring (≥ 3) bouts of CDI. CDI is currently the leading cause of healthcare associated infections in the United States. FMT has proven to have a high efficacy in antibiotic refractory recurrent CDI cases. Comparing the effectiveness of different types of transplantation and the kinetics of gut bacterial diversity transition from baseline to thirty days post transplantation revealed that the fresh and frozen microbiota diversity stabilized by day 7 and did not alter much further until day 30 after FMT. The lyophilized FMT recipients had a lower diversity at day 7 post FMT yet showed a sustained staggered increase in diversity and attained levels comparable to fresh and frozen FMT product recipients 30 days post FMT thus helping shed light upon the product handling and community differences that contribute to restoration of a microbial homeostasis in the gut.
Shah, Manasi S, "The gut microbiome as a modifiable risk factor in recurring communicable and chronic non-communicable intestinal diseases" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10250029.