Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease

Cell Host Microbe. 2020 Sep 9;28(3):422-433.e7. doi: 10.1016/j.chom.2020.07.020. Epub 2020 Aug 20.

Abstract

Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals disease-specific patterns. The IBD group shows increased concentrations of markers of inflammation and tissue damage compared with healthy controls, and metabolic changes associate with susceptibility to CDI. In IBD + CDI, we detect both metabolites associated with inflammation/tissue damage and fermentation products produced by C. difficile. The most discriminating metabolite found is isocaproyltaurine, a covalent conjugate of a distinctive C. difficile fermentation product (isocaproate) and an amino acid associated with tissue damage (taurine), which may be useful as a joint marker of the two disease processes.

Keywords: Clostridioides difficile; Gram-positive; inflammatory bowel disease; isocaproate; isocaproyltaurine; metabolome; microbiome; taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers
  • Caproates / metabolism*
  • Child
  • Clostridioides difficile / genetics
  • Clostridioides difficile / metabolism*
  • Clostridium Infections / complications*
  • DNA, Bacterial
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome
  • Humans
  • Inflammatory Bowel Diseases / complications*
  • Inflammatory Bowel Diseases / microbiology
  • Male
  • Metabolome*
  • Metagenomics*
  • Taurine / metabolism*

Substances

  • Biomarkers
  • Caproates
  • DNA, Bacterial
  • Taurine
  • isocaproic acid