A source for healthcare professionals to access the latest data and information on the diagnosis, treatment and management of patients with gut related disorders


Pathophysiology of bile acid diarrhoea (Part I)

Professor Julian R.F. Walters

Consultant Gastroenterologist and Professor of Gastroenterology, Imperial College London, London, UK

Bile acid diarrhoea (BAD) has been known historically as bile acid malabsorption (BAM). In patients with ileal disease or resection, BAD is secondary to malabsorption of bile acids, and this is also the case in certain other gastrointestinal disorders and after cholecystectomy. However, in the case of diarrhoea due to primary or idiopathic BAD, an obvious defect in absorption of bile acids is usually not observed. Instead in these cases, there is often greater bile acid synthesis; this overproduction results in greater concentrations of bile acids entering the colon, leading to diarrhoea.1

The synthesis of bile acids in the liver is regulated by negative feedback via fibroblast growth factor 19 (FGF19), produced in the ileum.2 Defects in the production of FGF19 could explain the pathology of primary BAD. It has been observed that serum FGF19 levels are lower in patients with BAD, compared to those without the disease (p<0.0001).3 In support of this proposed mechanism, it has been shown that low FGF19 levels in patients with BAD are related to increased bile acid synthesis, as measured by assay of the bile acid precursor, 7α-hydroxy-4-cholesten-3-one.4

A prospective study analysed a large patient group with chronic diarrhoea. Those with SeHCAT retention values >15% were used as controls and compared with patients with BAD, who had SeHCAT retention values ≤15%. Subgroup analyses looked at those with severe (SeHCAT <5%), moderate (SeHCAT 5–10%) and mild (SeHCAT 10–15%) BAD. The results showed a significant difference in the median FGF19 value in the patients with BAD compared with that in the control patients without BAD (p<0.006).4 In an analysis of the clinical features in the primary BAD group, the predominance of women was lower in the BAD group than in the control group. The groups were difficult to separate on clinical grounds, although the median number of daily stools in the primary BAD group (6/day) was slightly more than in controls or secondary BAD groups. The median duration of diarrhoea was 24 months in the primary BAD group. This study additionally revealed that low FGF19 values were predictive of the response to the various bile acid sequestrants.4


Professor Julian R.F. Walters is a Consultant Gastroenterologist and Professor at Imperial College London, London, UK. Professor Walters has contributed to more than 140 studies related to molecular and cellular function of the small intestine, in particular how the development and differentiation of the mucosal epithelial cells affects nutrient transport. This includes the effects of inflammatory diseases of the intestine causing malabsorption, such as coeliac disease and Crohn's disease, and the changes in gene expression during active disease and the repair process.


1. Van Tilburg AJ et al. Gut 1991;32:500–503.
2. Inagaki T et al. Cell Metab 2005;2:217–225.
3. Walters JR et al. Clin Gastroenterol Hepatol 2009;7:1189–1194.
4. Pattni SS  et al. Aliment Pharmacol Ther 2013;38:967–976.

Job number: JB57410GBl Date of Preparation: June 2019

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