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Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome
Open accessAbstract
The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.
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“However, an integrated longitudinal multi-omics analysis of the gut microbiome, metabolome, host epigenome and transcriptome, in the context of host symptoms and physiology in patients with IBS-D and IBS-C, identified subtype-specific and symptom-related variations in microbial composition and function.76”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [76]
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Metadata
- Authors
- Mars, R. A. T., Yang, Y., Ward, T., Houtti, M., Priya, S., Lekatz, H. R., Tang, X., Sun, Z., Kalari, K. R., Korem, T., Bhattarai, Y., Zheng, T., Bar, N., Frost, G., Johnson, A. J., van Treuren, W., Han, S., Ordog, T., Grover, M., Sonnenburg, J., D’Amato, M., Camilleri, M., Elinav, E., Segal, E., Blekhman, R., Farrugia, G., Swann, J. R., Knights, D., & Kashyap, P. C.
- Affiliations
- Mayo Clinic (US)
- Imperial College London (GB)
- University of Minnesota (US)
- Canadian Institute for Advanced Research (CA)
- Monash University (AU)
- Weizmann Institute of Science (IL)
- Stanford University (US)
- German Cancer Research Center (DE)
- University of Southampton (GB)
- Corresponding author
- Knights, Dan
- Kashyap, Purna C.
- ORCID
- Mars, Ruben A.T.
- Houtti, Mo
- Priya, Sambhawa
- Tang, Xiaojia
- Sun, Zhifu
- Kalari, Krishna R.
- Korem, Tal
- Bhattarai, Yogesh
- Zheng, Tenghao
- Frost, Gary
- Johnson, Abigail J.
- Han, Shuo
- Ordog, Tamas
- Grover, Madhusudan
- Sonnenburg, Justin
- D’Amato, Mauro
- Camilleri, Michael
- Elinav, Eran
- Segal, Eran
- Blekhman, Ran
- Farrugia, Gianrico
- Swann, Jonathan R.
- Knights, Dan
- Kashyap, Purna C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 182
- Issue
- 6
- Pages
- 1460-1473.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8109273
- OpenAlex
- W3084404023
- Cited by
- 456
- References
- 49
- Citations by year
- 2026: 59 · 2025: 69 · 2024: 99 · 2023: 78 · 2022: 92 · 2021: 53 · 2020: 5
- FWCI
- 18.48
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-11-12)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- irritable bowel syndrome, gut microbiota, microbial metabolites, purine metabolism, host-microbe interactions, IBS subtypes, host transcriptome, host metabolome, chronic gastrointestinal diseases, therapeutic target
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Animals, Bile Acids and Salts, Biopsy, Butyrates, Chromatography, Liquid, Cross-Sectional Studies, Feces, Female, Gene Expression Regulation, Humans, Longitudinal Studies, Male, Prospective Studies, Purines, Software, Hypoxanthine, Irritable Bowel Syndrome, Mice, Tandem Mass Spectrometry, Metabolome, Epigenomics, Transcriptome, Observational Studies as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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