title: Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea.
abstract: OBJECTIVE
  Variations in genes that regulate bile acid (BA) synthesis are associated with colonic transit in patients with irritable bowel syndrome (IBS). We investigated features of BA synthesis and excretion and genetic features of patients with different types of IBS.
  
  
  METHODS
  In 26 healthy volunteers, 26 patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D), we measured serum levels of 7α-hydroxy-4-cholesten-3-one (C4; a surrogate for BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that downregulates BA synthesis). For stool samples, we measured concentration of BA, weight, and amount of fat when participants were given high-fat diets. Spearman correlations were used to explore relationships among factors. We analyzed 1 polymorphism in Klotho-β (KLB) and 3 in fibroblast growth factor receptor-4 (FGFR4) for all members of each group using analysis of covariance.
  
  
  RESULTS
  The concentration of BA in stool was associated with group (for a comparison of 3 groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017). The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum levels of C4, compared with healthy volunteers. Serum level of C4 correlated with stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = -0.324; P = .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P < .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001) and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was associated with stool level of BA (P = .032).
  
  
  CONCLUSIONS
  Patients with IBS-D have greater body mass index and synthesize and excrete higher levels of BA than individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to identify patients with IBS-D who have BA malabsorption; studies are needed to determine if some patients have a genetic predisposition to this disorder.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Banny S
authors.initials: BS
authors.lastname: Wong
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.forename: Sanna
authors.initials: S
authors.lastname: McKinzie
authors.forename: Irene
authors.initials: I
authors.lastname: Busciglio
authors.forename: Olga
authors.initials: O
authors.lastname: Bondar
authors.forename: Roy B
authors.initials: RB
authors.lastname: Dyer
authors.forename: Jesse
authors.initials: J
authors.lastname: Lamsam
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002783:Cholestenones / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced*; D005243:Feces / Q000737:chemistry; D005346:Fibroblast Growth Factors / Q000097:blood; D005966:Glucuronidase / Q000235:genetics; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications*; D000090265:Klotho Proteins; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics; D044967:Serum / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; C117476:FGF19 protein, human; C002656:7 alpha-hydroxy-4-cholesten-3-one; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4; D005966:Glucuronidase; D000090265:Klotho Proteins