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.
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-Dpatients 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-Dpatients 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-Dpatients. IBS-D subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1 ng/ml. RESULTS:IBS-Dpatients 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-Dpatients 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. BAdiarrhea is identified more effectively with total fecal BA than with serum C4.
Authors: Paul Enck; Qasim Aziz; Giovanni Barbara; Adam D Farmer; Shin Fukudo; Emeran A Mayer; Beate Niesler; Eamonn M M Quigley; Mirjana Rajilić-Stojanović; Michael Schemann; Juliane Schwille-Kiuntke; Magnus Simren; Stephan Zipfel; Robin C Spiller Journal: Nat Rev Dis Primers Date: 2016-03-24 Impact factor: 52.329
Authors: Ian M Johnston; Jonathan D Nolan; Sanjeev S Pattni; Richard N Appleby; Justine H Zhang; Sarah L Kennie; Gaganjit K Madhan; Sina Jameie-Oskooei; Shivani Pathmasrirengam; Jeremy Lin; Albert Hong; Peter H Dixon; Catherine Williamson; Julian R F Walters Journal: Am J Gastroenterol Date: 2016-02-09 Impact factor: 10.864
Authors: M Camilleri; A Acosta; I Busciglio; A Boldingh; R B Dyer; A R Zinsmeister; A Lueke; A Gray; L J Donato Journal: Aliment Pharmacol Ther Date: 2015-01-16 Impact factor: 8.171