Circulating levels of PYY are increased in individuals with bile acid diarrhoea.

Abstract

Bile acid diarrhoea (BAD) is a chronic disease caused by a disturbance of the enterohepatic circulation resulting in an abundance of bile acids in the colon, which in turn causes diarrhoea. Since bile acids stimulate the secretion of the hormone peptide YY (PYY), we investigated PYY levels in plasma samples from earlier studies enrolling patients with BAD and healthy volunteers. We analysed total PYY in 1) a case-control study comparing individuals with BAD with matched healthy controls during acute administration of the bile acid sequestrant colesevelam and placebo; 2) a randomised controlled trial comparing the treatment effects of colesevelam and the glucagon-like peptide 1 (GLP-1) analogue liraglutide on bowel movements in individuals with BAD; and 3) a sequestrant study investigating the effect of treatment cessation in patients with BAD. We also investigated the PYY/GLP-1 ratios along the intestines of healthy individuals based on mRNA expression and immunohistochemistry. Individuals with BAD had higher fasting plasma PYY levels compared with controls but similar postprandial increments in the two groups. Symptom-alleviating treatment of BAD with sequestrants or liraglutide resulted in a decline of fasting PYY levels. Fasting PYY levels correlated positively with 7α-hydroxy-4-cholesten-3-one (C4) and plasma total bile acids. Finally, the PYY/GLP-1 ratio increased along the intestine with the highest ratios observed in the colon. Collectively, these results suggest a role for PYY as a marker for BAD pathophysiology and warrant further studies into the role of PYY in BAD and other diarrhoeal diseases.