Missing link identified: GpBAR1 is a neuronal bile acid receptor

In addition to their classical functions in aiding the digestion and absorption of lipids, bile acids are increasingly gaining appreciation for their roles in regulating intestinal physiology. Bile acids are now widely considered as hormones that exert a wide range of physiological and pathophysiological effects both within and outside the gastrointestinal (GI) tract. The discovery of the bile acid receptor, GpBAR1, represented a major step forward in our understanding of how cells can sense and respond to bile acids. GpBAR1 is a cell surface G protein-coupled receptor expressed on adipose tissue and skeletal muscle where it has been found to be an important regulator of cellular metabolism. In a paper published in the current issue of Neurogastroenterology and Motility, Poole et al. investigated the expression and function of GpBAR1 in mouse intestine. They found the receptor to be expressed throughout the GI tract but predominantly on nerves within the myenteric and submucosal plexuses. Employing in vitro and in vivo techniques they demonstrated that activation of GpBAR1 by bile acids inhibits small and large intestinal motor function and delays intestinal transit. The effects of GpBAR1 activation are mediated through activation of cholinergic and nitrergic interneurons. The data reported by Poole et al. provides novel and exciting insights into how bile acids exert their actions in the intestine. This Editorial Viewpoint aims to further consider the potential physiological and pathophysiological implications of their findings.