Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon
Open accessAbstract
Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic inflammation and suggest that microbial metabolism of UDCA is necessary for the full expression of its protective actions. NEW & NOTEWORTHY On the basis of its cytoprotective and anti-inflammatory actions, the secondary bile acid ursodeoxycholic acid (UDCA) has well-established uses in both traditional and Western medicine. We identify a new role for the primary metabolite of UDCA, lithocholic acid, as a potent inhibitor of intestinal inflammatory responses, and we present data to suggest that microbial metabolism of UDCA is necessary for the full expression of its protective effects against colonic inflammation.
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Activation of TGR5 is generally associated with anti-inflammatory effects and protective features towards the intestinal epithelium.
“Activation of TGR5 has generally been associated with anti-inflammatory effects and protective features towards the intestinal epithelium (Sarathy et al., 2017;Ward et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Ward et al., 2017
The available indexed passages are publication metadata and the paper’s title, which identifies anti-inflammatory actions of two bile acids but does not address TGR5 activation or epithelial protection. Searches for TGR5 and bile-acid receptor effects returned no substantive passage establishing the attributed claim. (LLM, conf=0.73)
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Interactive relationships between intestinal flora and bile acids
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- Authors
- Ward, J. B. J., Lajczak, N. K., Kelly, O. B., O’Dwyer, A. M., Giddam, A. K., Ní Gabhann, J., Franco, P., Tambuwala, M. M., Jefferies, C. A., Keely, S., Roda, A., & Keely, S. J.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- University of Newcastle Australia (AU)
- Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland;
- University of Bologna (IT)
- University of Ulster (GB)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Keely, Stephen J.
- ORCID
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2017-06-01
- Volume
- 312
- Issue
- 6
- Pages
- G550-G558
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2598445433
- Cited by
- 286
- References
- 6
- Citations by year
- 2026: 22 · 2025: 31 · 2024: 59 · 2023: 43 · 2022: 47 · 2021: 31 · 2020: 20 · 2019: 20 · 2018: 9 · 2017: 3
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- green
- pure.ulster.ac.uk
- Licence
- other-oa
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Ulster University Research Portal (Ulster University) (publishedVersion, other-oa)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Figshare (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Science Foundation Ireland (SFI) (10/IN.1/B2983)
- Crohns and Colitis Foundation of America (354322)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and biological activity of medicinal plants
- Keywords
- ursodeoxycholic acid, lithocholic acid, bile acids, inflammatory bowel disease, colonic inflammation, anti-inflammatory activity, colonic epithelial cells, inflammatory cytokines, DSS-induced colitis, TNF-α, interleukin-6, IL-1β, interferon-gamma
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Inflammatory Agents, Bacteria, Biotransformation, Colitis, Colon, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Intestinal Mucosa, Lithocholic Acid, Male, Mice, Inbred C57BL, Time Factors, Ursodeoxycholic Acid, Cytokines, Dextran Sulfate, Inflammation Mediators, HT29 Cells
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