Increased Bile Acid Biosynthesis Is Associated With Irritable Bowel Syndrome With Diarrhea

Abstract

BACKGROUND & AIMS 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.

High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients With Diarrhea-Predominant Irritable Bowel Syndrome Based on Rome III Criteria

“…We therefore believe that, having used state of the art definitions and testing modalities, our findings are contemporary and provide compelling evidence that can be generalized to other centers seeing a similar population of patients. In fact, a recent study from the United States identified that 38% of patients with D-IBS were noted to have higher serum C4, and faecal bile acids, compared with healthy volunteers, or patients with constipation-predominant IBS 27 suggesting that, if 75 SeHCAT testing were available in the USA, the yield in patients with D-IBS is likely to be similar to ours.…”

Alpha-2-adrenergic receptor gene polymorphism in Turkish population with irritable bowel syndrome

“…B3-adrenoceptor, cholinergic receptor muscarinic 3 polymorphisms, and tryptophan hydroxylase gene polymorphisms were also studied in IBS patients (27,28). Very recent studies about D-IBS patients address the genes regulating hepatic bile acid synthesis but more studies are needed to state an association (29,30).…”

Diarrea pos colecistectomía, enfoque diagnóstico y terapéutico

“…En los enterocitos del íleon, la unión de los AB con el FXR lleva a inducción transcripcional del factor de crecimiento del fibroblasto 19 (FGF19); la unión del FGF19 al receptor de membrana del hepatocito FGF tipo 4 (FGFR4) y su correceptor Klothob, activa vías intracelulares que disminuyen la expresión de CYP7A1 (11,20), esto es un ejemplo claro de retroalimentación negativa hígado-íleon. Se ha encontrado en distintos estudios, que explican el posible mecanismo de mala-absorción de AB, niveles bajos de FGF19 en pacientes con mala-absorción idiopática de AB e inversión de la relación FGF19 y 7 α-hidroxi-4-colesten-3-ona (C4), este último es un indicador de la síntesis de AB (21,22).…”