Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease
Open accessAbstract
Objective: Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Design: Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Results: Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 −13 ). Conclusions: We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.
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SCFAs are important metabolites of the gut microbiota, produced by the anaerobic fermentation of indigestible polysaccharides in the colon, and consist mainly of acetate (40%−60%), propionate (20%−25%), and butyrate (15%−20%).
“SCFAs are important metabolites of the gut microbiota, produced by the anaerobic fermentation of indigestible polysaccharides (e.g., dietary fiber and resistant starch) in the colon, and consist mainly of acetate (40%−60%), propionate (20%−25%), and butyrate (15%−20%) (53).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [53]
Interaction between the host genome and the gut microbiota affects the normal signaling of the GBA, and gene variants can regulate the gene-editing system of the natural gut flora and influence the enterobacterial composition.
“Interaction between the host genome and the gut microbiota (53) affects the normal signaling of the GBA, and gene variants can regulate the gene-editing system of the natural gut flora and influence the enterobacterial composition.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [53]
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- Authors
- Imhann, F., Vich Vila, A., Bonder, M. J., Fu, J., Gevers, D., Visschedijk, M. C., Spekhorst, L. M., Alberts, R., Franke, L., van Dullemen, H. M., Ter Steege, R. W. F., Huttenhower, C., Dijkstra, G., Xavier, R. J., Festen, E. A. M., Wijmenga, C., Zhernakova, A., & Weersma, R. K.
- Affiliations
- University Medical Center Groningen (NL)
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Broad Institute (US)
- Corresponding author
- Weersma, Rinse K
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2016-10-08
- Volume
- 67
- Issue
- 1
- Pages
- 108-119
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5699972
- OpenAlex
- W2529692498
- Cited by
- 788
- References
- 49
- Citations by year
- 2026: 38 · 2025: 77 · 2024: 88 · 2023: 90 · 2022: 101 · 2021: 116 · 2020: 103 · 2019: 85 · 2018: 55 · 2017: 30 · 2016: 2 · 2015: 1
- FWCI
- 29.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Rijksuniversiteit Groningen
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (917.14.374, 016.136.308)
- Universitair Medisch Centrum Groningen
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- 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
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Keywords
- inflammatory bowel disease, gut microbiota, host genetics, polygenic risk score, NOD2, CARD9, ATG16L1, IRGM, FUT2, Roseburia, Crohn's disease, disease location, ileal Crohn's disease, colonic Crohn's disease, microbial diversity, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Adult, Colitis, Ulcerative, Crohn Disease, Feces, Female, Humans, Male, Middle Aged, Severity of Illness Index, Inflammatory Bowel Diseases, Case-Control Studies, Risk Assessment, Genetic Predisposition to Disease, Host-Pathogen Interactions, Dysbiosis
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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