Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS

Objective Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. Design We measured Se-75-labelled homocholic acid-taurine ((75)SeHCAT) retention, and serum levels of 7 alpha-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects ((75)SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with (75)SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Results Compared with controls, patients with IBS had lower (75)SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal (75)SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with (75)SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220 +/- 109 vs 277 +/- 106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief >= 50% of weeks 5-8). Conclusions Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.