Effect of Increased Bile Acid Synthesis or Fecal Excretion in Irritable Bowel Syndrome-Diarrhea
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OBJECTIVES: Approximately 25% of patients with irritable bowel syndrome-diarrhea (IBS-D) have increased total fecal bile acids (BA) and serum C4 (surrogate for BA synthesis). BA synthesis-related genes (KLB and FGFR4) are associated with colonic transit (CT) in IBS-D. Our aims were: (i) to compare phenotype and pathophysiology in IBS-D patients with increased or normal fecal excretion or synthesis of BA; and (ii) to explore association of variations in two candidate bile-acid synthesis genes (KLB and FGFR4) in these two subgroups of IBS-D. METHODS: A total of 64 IBS-D patients underwent on one occasion: fasting serum C4 and FGF19, total fecal fat and BA excretion, CT, intestinal and colonic permeability, and candidate genotyping (rs17618244 (KLB), rs351855 (FGFR4)). Colonic sensation and tone were measured in 47 of the IBS-D patients. IBS-D subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1 ng/ml. RESULTS: IBS-D patients with fecal BA >2,337 mM per 48 h (19/54) had significantly greater body mass index, fecal fat, percent chenodeoxycholic acid (CDCA) in feces, and intestinal permeability, and borderline increased CT (P=0.13). Those IBS-D patients with serum C4 >47.1 ng/ml (13/54) had increased total fecal BA excretion and borderline increased colonic permeability. Variants in genes involved in feedback regulation of BA synthesis (KLB, P=0.06 and FGFR4, P=0.09) were potentially associated with the subgroup with elevated serum C4. CONCLUSIONS: IBS-D with increased BA excretion or synthesis is associated with significant pathophysiological changes relative to patients with normal BA profile. BA diarrhea is identified more effectively with total fecal BA than with serum C4.
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This may promote activation of immune cells, including T-lymphocytes and mast cells, in the gastrointestinal epithelium, leading to cytokine release, which can modify neural control of gastrointestinal motor, sensory, and secretory functions.
“This may promote activation of immune cells, including T-lymphocytes and mast cells, in the gastrointestinal epithelium, 52 leading to cytokine release, which can modify neural control of gastrointestinal motor, sensory, and secretory functions.”
From Irritable bowel syndrome (2020) · cites this paper as [52]
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- Authors
- Camilleri, M., Busciglio, I., Acosta, A., Shin, A., Carlson, P., Burton, D., Ryks, M., Rhoten, D., Lamsam, J., Lueke, A., Donato, L. J., & Zinsmeister, A. R.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Camilleri, Michael
- Venue
- American Journal of Gastroenterology
- Published
- 2014-10
- Volume
- 109
- Issue
- 10
- Pages
- 1621-1630
- ISSN
- 0002-9270 (ISSN-L)
- PMC
- PMC6994231
- OpenAlex
- W1971384756
- Cited by
- 114
- References
- 54
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 18 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 2 · 2016: 13 · 2015: 10 · 2014: 2
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- National Institutes of Health (UL1TR000135, UL1TR000448)
- Center for Clinical and Translational Science, Mayo Clinic
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK92179, R01DK092179, T32DK007130)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- bile acid synthesis, fecal bile acids, colonic transit, intestinal permeability, KLB, FGFR4, genetic variants, colonic tone, body mass index, fecal fat
- MeSH terms
- Klotho Proteins, Adult, Bile Acids and Salts, Cholestenones, Diarrhea, Feces, Female, Fibroblast Growth Factors, Gastrointestinal Transit, Humans, Male, Membrane Proteins, Middle Aged, Irritable Bowel Syndrome, Receptor, Fibroblast Growth Factor, Type 4
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