Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome

Abstract

Background: About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.

Aims: To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam.

Methods: A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4.

Results: Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat.

Conclusions: Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Figure 1

Experimental design of the two phases of the study which were of equal duration: during baseline, no medication was taken; in the treatment phase, patients received colesevelam, 1.875g b.i.d. for 10 days.

Figure 2

Comparison of (A) total fecal bile acid excretion over 48 hours during baseline and colesevelam treatment in the 12 patients individually (right panel) and as a group (left panel). Figures 2 (B) and (C) show individual data during baseline and colesevelam treatment for total fecal bile acid excretion per gram of stool, and fasting serum C4 respectively.

Figure 3

Changes in percentage of deoxycholic acid (DCA) and cholic acid (CA) in stool with colesevelam, suggesting that the medication sequesters the secretory, dehydroxylated secondary bile acid, DCA, which is derived from the primary bile acid, CA. There were no significant differences in lithocholic acid or chenodeoxycholic acid in stool.

Figure 4

Effect of colesevelam on fecal fat in patients with diarrhea-predominant irritable bowel syndrome and bile acid malabsorption.

Figure 5

Effects of colesevelam on (A) stool form [Bristol Stool Form Scale (BSF scale)] and (B) stool frequency per week in patients with diarrhea-predominant irritable bowel syndrome and bile acid malabsorption.

Figure 6

Significant inverse correlation between the fecal excretion of total bile acids and number of bowel movements (BM) per week, suggesting that sequestration of the bile acids by colesevelam reduced the diarrhea.

Figure 7

Concordance between mean total fecal bile acid (BA) excretion in all samples from an individual patient, and the total fecal BA content in a randomly selected individual sample.