Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease.

Peter Hegyi, Joszef Maléth, Julian R Walters, Alan F Hofmann, Stephen J Keely

Journal: Physiological reviews 2019;98(4):1983-2023

PMID: 30067158

Plain Language Summary

Bile acids are bioactive bacterial metabolites which recent research shows may be helpful in protecting the epithelial cells which line the entire surface of the gastrointestinal tract. Many conditions such as inflammatory bowel disease, chronic diarrhoea, pancreatitis, reflux esophagitis, and cancer are influenced by the integrity of the intestinal lining and/or disruption of epithelial transport; the movement of digestive enzymes, nutrients, electrolytes, and fluids. Bile acids are now being further studied as a new target for therapies to help these conditions. Typically, bile acids help with the digestion of fats. These acids are created in the liver and stored in the gall bladder and transported throughout the small and large intestines where they support the cells in the intestinal lining. This is the same lining which acts as a barrier to external pathogens and toxins. All the conditions above appear to show alterations in bile acid activity indicating a role for therapeutic targeting of bile acids in intestinal disease. This may include dietary manipulation, probiotics and fecal transfers to support bile acid production and function.

Abstract

Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer. Driven by discovery of specific receptors on intestinal epithelial cells, new insights into mechanisms that control their synthesis and enterohepatic circulation, and a growing appreciation of their roles as bioactive bacterial metabolites, bile acids are currently receiving a great deal of interest as critical regulators of epithelial function in health and disease. This review aims to summarize recent advances in this field and to highlight how bile acids are now emerging as exciting new targets for disease intervention.

Address: Momentum Translational Gastroenterology Research Group, Hungarian Academy of Sciences-University of Szeged , Szeged , Hungary ; Institute for Translational Medicine, Medical School, University of Pécs , Pécs , Hungary ; Momentum Epithelial Cell Signalling and Secretion Research Group and First Department of Medicine, University of Szeged , Szeged , Hungary ; Division of Digestive Diseases, Department of Gastroenterology, Hammersmith Hospital, Imperial College London , London , United Kingdom ; Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California ; and Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin , Ireland.

DOI: 10.1152/physrev.00054.2017