Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients

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...

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Published in:Inflammatory bowel diseases 2020-02, Vol.26 (3), p.347-359
Main 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
Format: Article
Language:English
Subjects:
Animals
Colony Count, Microbial
Crohn Disease - therapy
Disease Models, Animal
Editor's Choice
Fecal Microbiota Transplantation
Feces - microbiology
Female
Gastrointestinal diseases
Gastrointestinal Microbiome - genetics
Humans
Ileitis - therapy
Inflammation
Leading Off
Male
Mice
Microbiota (Symbiotic organisms)
Remission Induction
RNA, Ribosomal, 16S - genetics
Transplantation of organs, tissues, etc
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Summary: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. 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.
ISSN:1078-0998
1536-4844
DOI:10.1093/ibd/izz242