Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients. Issue 3 (21st November 2019)

• Record Type: Journal Article
• Authors: Basson, Abigail R; Gomez-Nguyen, Adrian; Menghini, Paola; Buttó, Ludovica F; Di Martino, Luca; Aladyshkina, Natalia; Osme, Abdullah; LaSalla, Alexandria; Fischer, Derek; Ezeji, Jessica C; Erkkila, Hailey L; Brennan, Connery J; Lam, Minh; Rodriguez-Palacios, Alexander; Cominelli, Fabio
• Is Part Of: Inflammatory bowel diseases. Volume 26:Issue 3(2020)
• Page Start: 347
• Page End: 359
• Publication Date: 2019-11-21
• Subjects: fecal microbiota transplantation -- autologous -- remission -- Crohn's disease -- amino acids -- biomarkers; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izz242
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Background: Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD. Methods: We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn's disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice). Results: Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn's or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD. Conclusion: The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients' best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups. Abstract : By conducting a series of fecal microbiota transplantation experiments, we show a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD.