Dataset Information

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 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.

SUBMITTER: Basson AR

PROVIDER: S-EPMC7012301 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Basson Abigail R AR Gomez-Nguyen Adrian A Menghini Paola P Buttó Ludovica F LF Di Martino Luca L Aladyshkina Natalia N Osme Abdullah A LaSalla Alexandria A Fischer Derek D Ezeji Jessica C JC Erkkila Hailey L HL Brennan Connery J CJ Lam Minh M Rodriguez-Palacios Alexander A Cominelli Fabio F

Inflammatory bowel diseases 20200201 3

<h4>Background</h4>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.<h4>Methods</h4>We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from ...[more]

PMID: 31750921

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Project description:Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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