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

41 Citations (Scopus)

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
JournalAmerican Journal of Gastroenterology
Volume109
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Fingerprint

Irritable Bowel Syndrome
Bile Acids and Salts
Diarrhea
Serum
Permeability
Fats
Genes
Chenodeoxycholic Acid
Feces
Fasting
Body Mass Index

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Camilleri, M., Busciglio, I., Acosta, A., Shin, A., Carlson, P., Burton, D., ... Zinsmeister, A. R. (2014). Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea. American Journal of Gastroenterology, 109(10), 1621-1630. https://doi.org/10.1038/ajg.2014.215

Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea. / Camilleri, Michael; Busciglio, Irene; Acosta, Andres; Shin, Andrea; Carlson, Paula; Burton, Duane; Ryks, Michael; Rhoten, Deborah; Lamsam, Jesse; Lueke, Alan; Donato, Leslie J.; Zinsmeister, Alan R.

In: American Journal of Gastroenterology, Vol. 109, No. 10, 01.10.2014, p. 1621-1630.

Research output: Contribution to journalArticle

Camilleri, M, Busciglio, I, Acosta, A, Shin, A, Carlson, P, Burton, D, Ryks, M, Rhoten, D, Lamsam, J, Lueke, A, Donato, LJ & Zinsmeister, AR 2014, 'Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea', American Journal of Gastroenterology, vol. 109, no. 10, pp. 1621-1630. https://doi.org/10.1038/ajg.2014.215
Camilleri, Michael ; Busciglio, Irene ; Acosta, Andres ; Shin, Andrea ; Carlson, Paula ; Burton, Duane ; Ryks, Michael ; Rhoten, Deborah ; Lamsam, Jesse ; Lueke, Alan ; Donato, Leslie J. ; Zinsmeister, Alan R. / Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea. In: American Journal of Gastroenterology. 2014 ; Vol. 109, No. 10. pp. 1621-1630.
@article{cb9600afe1d64d6dbb33d6060a37183f,
title = "Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea",
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.",
author = "Michael Camilleri and Irene Busciglio and Andres Acosta and Andrea Shin and Paula Carlson and Duane Burton and Michael Ryks and Deborah Rhoten and Jesse Lamsam and Alan Lueke and Donato, {Leslie J.} and Zinsmeister, {Alan R.}",
year = "2014",
month = "10",
day = "1",
doi = "10.1038/ajg.2014.215",
language = "English (US)",
volume = "109",
pages = "1621--1630",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea

AU - Camilleri, Michael

AU - Busciglio, Irene

AU - Acosta, Andres

AU - Shin, Andrea

AU - Carlson, Paula

AU - Burton, Duane

AU - Ryks, Michael

AU - Rhoten, Deborah

AU - Lamsam, Jesse

AU - Lueke, Alan

AU - Donato, Leslie J.

AU - Zinsmeister, Alan R.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84924925529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924925529&partnerID=8YFLogxK

U2 - 10.1038/ajg.2014.215

DO - 10.1038/ajg.2014.215

M3 - Article

C2 - 25070056

AN - SCOPUS:84924925529

VL - 109

SP - 1621

EP - 1630

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 10

ER -