Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome

Abstract

Background & aims: There is an unclear relationship among bowel symptoms, excretion of unconjugated fecal bile acid (UBA), and colonic transit in irritable bowel syndrome (IBS). We measured total and main individual UBA in fecal samples of patients with IBS and assessed relationships among stool frequency or consistency, fecal UBA (total and individual), and colonic transit.

Methods: In this study 30 healthy volunteers (controls), 31 subjects with IBS with diarrhea (IBS-D), and 30 with IBS with constipation (IBS-C) were placed on 4-day diets containing 100 g fat; we measured stool characteristics, total fecal UBA and fat levels, and overall colonic transit. We assessed univariate associations of total and individual levels of fecal UBA with phenotype (controls, IBS-D, IBS-C) by using the Kruskal-Wallis test; associations between end points were assessed by using Spearman correlations. With response surface regression models, we assessed relationships between stool, colonic transit, and fecal total and secretory UBA.

Results: There was a significant association between total fecal UBA and phenotype (P = .029); the association was greater for IBS-D than IBS-C, compared with controls. Fecal levels of primary UBAs (cholic and chenodeoxycholic acids) were higher in subjects with IBS-D, compared with controls (both P < .01). Levels of fecal secretory UBAs (chenodeoxycholic acid, P = .019; deoxycholic acid, P = .025) were lower in subjects with IBS-C compared with controls, whereas levels of the nonsecretory UBA, lithocholic acid, were higher (P = .020). There were significant univariate associations between stool number and form and total fecal UBA (including percentages of lithocholic acid, chenodeoxycholic acid and cholic acid), fecal fat, and colonic transit at 24 and 48 hours after eating. In the regression models, the relative contribution of colonic transit was consistently greater and largely independent of the contribution of bile acids.

Conclusions: Measurements of individual UBAs identify changes associated with stool characteristics in patients with IBS; these effects are independent of the effects of colonic transit.

Keywords: Abdominal Pain; BA; C; CA; CDCA; CT; Constipation; D; DCA; Diarrhea; FGID; GC; HAD; HV; Hospital Anxiety and Depression Scale; IBS; LCA; Secretory; UBA; UDCA; bile acid; chenodeoxycholic acid; cholic acid; colonic transit; constipation; deoxycholic acid; diarrhea; functional gastrointestinal disorder; geometric center; healthy volunteers; irritable bowel syndrome; lithocholic acid; unconjugated bile acid; ursodeoxycholic acid.

Figure 1

Comparison of total 48-hour stool unconjugated bile acids (UBA) in the three phenotype subgroups [constipation-predominant irritable bowel syndrome (IBS-C), diarrhea-predominant irritable bowel syndrome (IBS-D), and healthy volunteers (HV)]. Data show median, interquartile range and 5–95^th percentile range, as well as outliers. There was a significant three-group (overall) association between total fecal UBA and phenotype group, but no significant differences between IBS-D or IBS-C and controls. Red data points denote patients with prior cholecystectomy.

Figure 2

Surface plots of relationship of stool number or form with total and secretory fecal unconjugated bile acids (BA) and colonic transit (CT) at 24 hours (GC24). Note that stool number and form increase with increased CT measurement (x axis) and with increased fecal unconjugated total or secretory BA (z axis) at low CT measurements. However, the surface plot shows that both stool number and form were lower when the CT was fastest and fecal BA highest.