title: Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea.
abstract: OBJECTIVE
  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.
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Michael
authors: M
authors: Camilleri
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Irene
authors: I
authors: Busciglio
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Andres
authors: A
authors: Acosta
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Andrea
authors: A
authors: Shin
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Paula
authors: P
authors: Carlson
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Duane
authors: D
authors: Burton
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Michael
authors: M
authors: Ryks
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Deborah
authors: D
authors: Rhoten
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Jesse
authors: J
authors: Lamsam
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Alan
authors: A
authors: Lueke
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Leslie J
authors: LJ
authors: Donato
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Alan R
authors: AR
authors: Zinsmeister
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002783:Cholestenones / Q000097:blood*; D003967:Diarrhea / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005243:Feces / Q000737:chemistry; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D005772:Gastrointestinal Transit / Q000502:physiology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000090265:Klotho Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics*
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; C117476:FGF19 protein, human; C538995:KLB protein, human; D008565:Membrane Proteins; C002656:7 alpha-hydroxy-4-cholesten-3-one; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4; D000090265:Klotho Proteins