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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2017; 23(36): 6593-6627
Published online Sep 28, 2017. doi: 10.3748/wjg.v23.i36.6593
New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond
Emanuele Sinagra, Gaetano Cristian Morreale, Ghazaleh Mohammadian, Giorgio Fusco, Valentina Guarnotta, Giovanni Tomasello, Francesco Cappello, Francesca Rossi, Georgios Amvrosiadis, Dario Raimondo
Emanuele Sinagra, Francesca Rossi, Dario Raimondo, Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
Emanuele Sinagra, Giovanni Tomasello, Francesco Cappello, Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
Emanuele Sinagra, Giovanni Tomasello, Francesco Cappello, Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
Gaetano Cristian Morreale, Georgios Amvrosiadis, Unit of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
Ghazaleh Mohammadian, Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Huddinge, 17176 Stockholm, Sweden
Giorgio Fusco, Unit of Internal Medicine, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
Valentina Guarnotta, Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo 90127, Italy
Author contributions: Sinagra E designed the study; Sinagra E, Mohammadian G, Amvrosiadis G, Rossi F, Morreale GC wrote the paper; Guarnotta V, Cappello F and Fusco G contributed to the revision of the manuscript; Tomasello G and Raimondo D supervised the work.
Conflict-of-interest statement: All the authors declare that this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors, thus disclosing any conflict of interests regarding such work.
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: Dr. Emanuele Sinagra, Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, snc, 90015 Cefalù, Italy. emanuelesinagra83@googlemail.com
Telephone: +39-92-1920712 Fax: +39-92-1920406
Received: February 2, 2017
Peer-review started: February 8, 2017
First decision: March 16, 2017
Revised: April 15, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: September 28, 2017
Processing time: 235 Days and 8.1 Hours
Abstract

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.

Keywords: Therapy; Low grade inflammation; Motility; Secretion; Irritable bowel syndrome; Immunoendocrine axis

Core tip: Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Despite there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. The understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in the treatment of IBS. This literature review aims to summarize the findings relating the new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.