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Effect of Increased Bile Acid Synthesis or Fecal Excretion in Irritable Bowel Syndrome-Diarrhea

Camilleri, Michael MD1; Busciglio, Irene BS1; Acosta, Andres MD, PhD1; Shin, Andrea MD, MS1; Carlson, Paula BS1; Burton, Duane BS1; Ryks, Michael1; Rhoten, Deborah1; Lamsam, Jesse MT (ASCP)2; Lueke, Alan BS2; Donato, Leslie J PhD2; Zinsmeister, Alan R PhD3

American Journal of Gastroenterology: October 2014 - Volume 109 - Issue 10 - p 1621–1630
doi: 10.1038/ajg.2014.215
Functional GI Disorders
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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 (KLBandFGFR4) 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 (KLBandFGFR4) 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 andFGFR4,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.

1 Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA

2 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

3 Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

Correspondence: Michael Camilleri, MD, Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic College of Medicine, Charlton 8-110, 200 First Street SW, Rochester, Minnesota 55905, USA. E-mail: camilleri.michael@mayo.edu

Received 2 April 2014; accepted 9 June 2014

published online 29 July 2014

© The American College of Gastroenterology 2014. All Rights Reserved.
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