Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease
- Frederic D. Bushman 10
- Maire Conrad
- Yue Ren
- Hongzhe Li
- Kyle Bittinger
- Robert Baldassano
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Highlights
- •Multi-omics reveals markers of CDI in pediatric IBD patients
- •Identification of metabolites reveals distinctive features for IBD and CDI
- •Isocaproyltaurine is made by C. difficile and associates with active IBD
- •Identifies biomarkers potentially useful for distinguishing disease processes
Summary
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.
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