New treatments and therapeutic targets for IBS and other functional bowel disorders

• Published in: Nature reviews. Gastroenterology & hepatology 2018-10, Vol.15 (10), p.589-605
• Main Authors: Simrén, Magnus, Tack, Jan
• Format: Article
• Language: English
• Subjects: 692/699/1503/1502; 692/699/1503/1581/2071; 692/699/1503/2753; 692/700/565; Acids; Bile; Bile acids; bile-acid; Biological markers; Biomedicine; Care and treatment; chronic idiopathic constipation; Clinical Medicine; Clinical trials; Diagnosis; Digestive system; Drug development; fecal microbiota transplantation; Gastric motility; Gastroenterology; Gastrointestinal tract; Health aspects; Hepatology; Hypersensitivity; Identification and classification; Immune response; Immune system; Immunosuppressive agents; international; intestinal bacterial overgrowth; Intestinal microflora; Intestine; Irritable bowel syndrome; Klinisk medicin; low fodmap diet; malabsorption; Medicine; Medicine & Public Health; Microbiota; Motility; Pain; Patients; Permeability; placebo-controlled trial; quality-of-life; randomized controlled-trial; Review Article; scientific association; Therapeutic applications
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/s41575-018-0034-5

Functional bowel disorders (FBDs) are a spectrum of disorders characterized by combinations of symptoms attributable to the lower gastrointestinal tract. Most current first-line therapies for IBS and other FBDs target the predominant symptom and mainly affect one symptom in the symptom complex. Additional broadly effective treatment alternatives targeting the entire symptom complex are needed. New drugs for FBDs (such as lubiprostone, linaclotide, plecanatide, prucalopride, eluxadoline and rifaximin) target key mechanisms in the pathophysiology of these disorders and improve both the abnormal bowel habit and other key symptoms, such as abdominal pain and bloating. The current development of new treatment alternatives is focusing on different aspects of the complex pathophysiology of IBS and other FBDs: gut microenvironment (via diet and modulation of gut microbiota), enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut–brain interactions, gut barrier function and the immune system within the gastrointestinal tract. Studies also suggest that personalized treatment of IBS and other FBDs is possible using various diagnostic markers. Current effective treatment options for IBS and other functional bowel disorders are limited. This Review focuses on new and emerging therapies that target the entire symptom complex in these common disorders. Key points Treatment options for functional bowel disorders (FBDs) target key pathophysiological factors along the gut–brain axis, including altered gastrointestinal motility, visceral hypersensitivity, increased intestinal permeability, immune activation and altered gut microbiota. Current first-line therapies for IBS and other FBDs mainly affect one symptom in the symptom complex, which is an inherent limitation. New drugs for FBDs target key pathophysiological mechanisms and differ from current therapies by improving the abnormal bowel habit as well as other symptoms, such as abdominal pain and bloating. Gut luminal factors, such as food, microbiota and bile acids, and their interaction with each other and the host might be important for symptom generation in at least a subset of patients with FBDs. Treatments affecting gastrointestinal motility and sensitivity, as well as gut barrier function, are promising; medical foods have also been tested in small trials in IBS, with a good safety profile and some efficacy. Personalized treatment strategies for patients with FBDs, based on