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Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease
Open accessAbstract
BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.
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“A study evaluating genetic variations in NR1H4 found no association between single-nucleotide polymorphisms in this gene and IBD risk (Nijmeijer et al., 2011).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Nijmeijer et al., 2011
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“…in the composition of the bile acid pool, an increase in colonic expression of GPBAR1, and a decrease in ileal activity of BAR have all been detected in patients suffering from IBD (Cipriani et al., 2011; Duboc et al., 2013; Lenz et al., 1976; Nijmeijer et al., 2011; Rutgeerts et al., 1979).”
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Metadata
- Authors
- Nijmeijer, R. M., Gadaleta, R. M., van Mil, S. W. C., van Bodegraven, A. A., Crusius, J. B. A., Dijkstra, G., Hommes, D. W., de Jong, D. J., Stokkers, P. C. F., Verspaget, H. W., Weersma, R. K., van der Woude, C. J., Stapelbroek, J. M., Schipper, M. E. I., Wijmenga, C., van Erpecum, K. J., Oldenburg, B., & on behalf of the Dutch Initiative on Crohn, C. (.
- Affiliations
- University Medical Center Utrecht (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- University Medical Center Groningen (NL)
- Leiden University Medical Center (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Oldenburg, Bas
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-22
- Volume
- 6
- Issue
- 8
- Pages
- e23745
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3161760
- OpenAlex
- W2119543164
- Cited by
- 119
- References
- 35
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 11 · 2021: 13 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 8
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- UvA-DARE (University of Amsterdam) (acceptedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Universiteit Utrecht
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- farnesoid X receptor, FXR activation, inflammatory bowel disease, Crohn's disease, ulcerative colitis, SHP, ileum, villin, genetic variation, single nucleotide polymorphisms, FXR agonists, intestinal inflammation
- MeSH terms
- Receptor, Farnesoid X-Activated, Colitis, Ulcerative, Colon, Female, Humans, Ileum, Male, RNA, Messenger, Genetic Variation, Inflammatory Bowel Diseases, Gene Expression, Case-Control Studies, Receptors, Cytoplasmic and Nuclear, Polymorphism, Single Nucleotide
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