Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2017; 23(9): 1513-1520
Published online Mar 7, 2017. doi: 10.3748/wjg.v23.i9.1513
P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers
Elke Cario
Elke Cario, Experimental Gastroenterology, Department of Gastroenterology and Hepatology, University Hospital Essen, Medical School, University of Duisburg-Essen, 45147 Essen, Germany
Author contributions: Cario E contributed all to this manuscript.
Supported by the Deutsche Forschungsgemeinschaft, No. CA226/4-3 to Cario E.
Conflict-of-interest statement: Cario E declares no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Elke Cario, MD, Professor, Experimental Gastroenterology, Department of Gastroenterology and Hepatology, University Hospital Essen, Medical School, University of Duisburg-Essen, Hufelandstr. 55, D-45122 Essen, 45147 Essen, Germany. elke.cario@uni-due.de
Telephone: +49-201-7234527 Fax: +49-201-7236858
Received: November 24, 2016
Peer-review started: November 27, 2016
First decision: December 19, 2016
Revised: January 6, 2017
Accepted: February 16, 2017
Article in press: February 17, 2017
Published online: March 7, 2017
Abstract

The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.

Keywords: Inflammatory bowel diseases, Multidrug resistance, Innate immunity, Microbiota, Xenobiotics

Core tip: Altered levels of p-glycoprotein (p-gp) expression as well as genetic variants of ABCB1/MDR1 have been associated with inflammatory bowel diseases (IBD). Decreased efflux activity of p-gp may promote disease susceptibility, while increased efflux activity may impair drug responses in IBD. In this Editorial, I highlight what we need to know about this transporter and xenobiotic signaling pathways in order to better understand its potential pathophysiology in IBD and develop targeted therapies.