FMT Manuscript

Published: 6 September 2024| Version 1 | DOI: 10.17632/ygbgt77whh.1
Contributor:
Sam McMillan

Description

Recurrent C. difficile infection (rCDI) is an urgent public health threat for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms which mediate a successful FMT are not well understood. Here we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT, in response to FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile salt hydrolases and baiA genesbile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid inducible (bai) operon, post-FMT. We also show changes in gut microbe encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to the biosynthesis of the amino acids C. difficile is auxotrophic for. LC-IMS-MS revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here we define the structural and functional changes associated with a successful FMT, and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota focused therapeutics to treat rCDI.

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Steps to reproduce

Shallow shotgun sequencing by Diversigen identified 447 microbial species and 1,060,171 microbial genes. Untargeted metabolomic analysis by Metabolon identified 924 unique metabolites. Lipidomics using LC-IMS-MS identified 130 unique bile acids and MCBAs in the stool samples Steps to reproduce data analysis located here: 10.5281/zenodo.12110446

Institutions

North Carolina State University

Categories

Metagenomics, Metabolomics, Gut Microbiota

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