Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea

Michael Camilleri, Irene Busciglio, Andres Acosta, Andrea Shin, Paula Carlson, Duane Burton, Michael Ryks, Deborah Rhoten, Jesse Lamsam, Alan Lueke, Leslie J. Donato, Alan R. Zinsmeister

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1621-1630
Number of pages10
JournalThe American journal of gastroenterology
Volume109
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    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. (2014). Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea. The American journal of gastroenterology, 109(10), 1621-1630. https://doi.org/10.1038/ajg.2014.215