Managing bile acid diarrhoea

Abstract

Bowel symptoms including diarrhoea can be produced when excess bile acids (BA) are present in the colon. This condition, known as bile acid or bile salt malabsorption, has been under recognized, as the best diagnostic method, the (75)Se-homocholic acid taurine (SeHCAT) test, is not available in many countries and is not fully utilized in others. Reduced SeHCAT retention establishes that this is a complication of many other gastrointestinal diseases. Repeated studies show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an estimated population prevalence of around 1%. Recent work suggests that the condition previously called idiopathic bile acid malabsorption (BAM) is not in fact due to a defect in absorption, but results from an overproduction of BA because of defective feedback inhibition of hepatic bile acid synthesis, a function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach to treatment currently depends on binding excess BA, to reduce their secretory actions, using colestyramine, colestipol and, most recently, colesevelam. Colesevelam has a number of potential advantages that merit further investigation in trials directed at patients with bile acid diarrhoea.

Keywords: Crohn's disease; SeHCAT; bile acids; colesevelam; colestipol; colestyramine; fibroblast growth factor 19; functional diarrhoea; irritable bowel syndrome; malabsorption.

Figure 1.

The enterohepatic circulation of bile acids. The various steps in bile acid synthesis, secretion, absorption and resecretion are indicated.

Figure 2.

Effects of specific changes affecting the enterohepatic circulation of bile acids on calculated ⁷⁵Se-homocholic acid taurine (SeHCAT) retention and faecal bile acid loss. Predicted results from a computer simulation model of bile acid kinetics are presented. SeHCAT retention (open symbols, left axis) and cumulative faecal bile acid loss (closed symbols, right axis) are shown over 7 days. The dashed line indicates 10% SeHCAT retention. (A) Typical normal values. (B) Effects of reducing bile acid absorption on each cycle from 95% to 90%. (C) Effects of increasing the number of cycles to 6/day from 4/day. (D) Effects of increasing the total bile acid pool size from 2 g to 2.8 g. Absorption is increased from 1.9 g to 2.6 g; the fractional absorption decreases slightly from 95% to 93%.