- Fecal Incontinence
|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.
Frederic D Bushman 1, Maire Conrad 2, Yue Ren 3, Chunyu Zhao 4, Christopher Gu 5, Christopher Petucci 6, Min-Soo Kim 6, Arwa Abbas 7, Kevin J Downes 8, Nina Devas 4, Lisa M Mattei 4, Jessica Breton 2, Judith Kelsen 2, Sarah Marakos 4, Alissa Galgano 4, Kelly Kachelries 4, Jessi Erlichman 4, Jessica L Hart 9, Michael Moraskie 4, Dorothy Kim 4, Huanjia Zhang 4, Casey E Hofstaedter 4, Gary D Wu 10, James D Lewis 10, Joseph P Zackular 7, Hongzhe Li 3, Kyle Bittinger 4, Robert Baldassano 2
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.