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

Author information

• ¹Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bushman@pennmedicine.upenn.edu.
• ²Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• ³Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• ⁴Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
• ⁵Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• ⁶Metabolomics Core, Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• ⁷Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
• ⁸Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• ⁹Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
• ¹⁰Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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.