Gut microbiome structure and metabolic activity in inflammatory bowel disease
Open accessAbstract
The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.
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Many functional metabolomics studies do not measure functional properties of the metabolites themselves but determine function using correlation and guilt by association with known bioactive metabolites, transcription, or protein expression.
“Many functional metabolomics studies do not measure functional properties of the metabolites themselves, but rather determine function using correlation and “guilt by association” with other known bioactive metabolites, transcription, or protein expression”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [16]
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Experimental — accuracy not yet measuredChanges in bile acid composition and concentrations are associated with metabolic disorders and inflammatory bowel disease, which increase colorectal cancer risk.
“Changes in bile acid composition and concentrations have been associated with metabolic disorders and IBD, which increases risk for CRC.161, 162”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [162]
Multiple lines of evidence point towards central roles of gut microbiome perturbations in the pathogenesis of IBD.
“Multiple lines of evidence point towards central roles of gut microbiome perturbations in the pathogenesis of IBD.”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [151]
GI metagenomes of IBD patients are markedly different from non-IBD controls, showing increased tolerance for oxidative stress and correlation with inflammatory markers.
“The GI metagenomes of IBD patients are also markedly different from non-IBD controls, showing an increased tolerance for oxidative stress and a correlation with inflammatory markers (Franzosa et al., 2019).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Franzosa et al., 2019
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Microbiota-gut brain axis involvement in neuropsychiatric disorders
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Viral Infections, the Microbiome, and Probiotics
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The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
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- Authors
- Franzosa, E. A., Sirota-Madi, A., Avila-Pacheco, J., Fornelos, N., Haiser, H. J., Reinker, S., Vatanen, T., Hall, A. B., Mallick, H., McIver, L. J., Sauk, J. S., Wilson, R. G., Stevens, B. W., Scott, J. M., Pierce, K., Deik, A. A., Bullock, K., Imhann, F., Porter, J. A., Zhernakova, A., Fu, J., Weersma, R. K., Wijmenga, C., Clish, C. B., Vlamakis, H., Huttenhower, C., & Xavier, R. J.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- University Medical Center Groningen (NL)
- Novartis (Switzerland) (CH)
- Corresponding author
- Huttenhower, Curtis
- Xavier, Ramnik J.
- ORCID
- Venue
- Nature Microbiology
- Published
- 2018-12-10
- Volume
- 4
- Issue
- 2
- Pages
- 293-305
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC6342642
- OpenAlex
- W2903406988
- Cited by
- 1,995
- References
- 57
- Citations by year
- 2026: 251 · 2025: 310 · 2024: 349 · 2023: 275 · 2022: 331 · 2021: 270 · 2020: 156 · 2019: 53
- FWCI
- 42.87
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-04-10)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- National Science Foundation (1053486, CAREER, 1453942)
- Crohn's and Colitis Foundation of America
- Crohn's and Colitis Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.13.013, 016.Vidi.178.056, SPI 92-266, 016.136.308)
- National Institutes of Health (DBI-1053486)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092405, R24DK110499, U54DK102557, U01DK097430, P30DK043351, P30DK040561)
- H2020 European Research Council (715772)
- FP7 Ideas: European Research Council (322698)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- inflammatory bowel disease, Crohn's disease, ulcerative colitis, gut microbiota, gut metabolome, fecal calprotectin, sphingolipids, bile acids, triglycerides, tetrapyrroles, oxidative stress, diagnostic biomarkers, therapeutic target
- MeSH terms
- Gastrointestinal Microbiome, Colitis, Ulcerative, Crohn Disease, Feces, Humans, Inflammation, Inflammatory Bowel Diseases, Biomarkers, Leukocyte L1 Antigen Complex, Biodiversity, Metagenome, Metabolome
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