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

Nature Reviews Gastroenterology & Hepatology volume 15, pages 589–605 (2018)Cite this article

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Abstract

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.

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 various diagnostic markers, seem possible in the not so distant future.

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Fig. 1: The pathophysiology of functional bowel disorders.
Fig. 2: Symptom generation after intake of foods rich in fermentable oligosaccharides, disaccharides, monosaccharides and polyols.
Fig. 3: The enterohepatic circulation of bile acids.
Fig. 4: Mechanisms of action of agents used for treatment of IBS-D and functional diarrhoea.
Fig. 5: Mechanisms of action of agents used for treatment of IBS-C and chronic constipation.

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Review criteria

This Review is based on literature searches performed in the PubMed database in August 2017 using the search terms “irritable bowel syndrome”, “functional bowel disorder”, “constipation”, “diarrhea”, “bloating”, “clinical trial”, “treatment”, “diet”, “probiotics”, “antibiotics”, “prebiotics”, “FMT”, “inflammation”, “prokinetics”, “microbiota”, “5-hydroxytryptamine”, “serotonin”, “secretagogue”, “herb” and “medical foods”. The reference lists of identified articles or linked articles were searched for further papers. English-language original research and review articles were considered. No publication date restrictions were applied. The Review is also based on the authors’ personal knowledge of ongoing clinical trials as well as on a search of Clinicaltrials.gov using the terms “irritable bowel syndrome”, “constipation” and “diarrhea”.

Reviewer information

Nature Reviews Gastroenterology & Hepatology thanks B. Niesler, E. Quigley and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Magnus Simrén

  2. Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA

    Magnus Simrén

  3. Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium

    Jan Tack

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Both authors contributed equally to all aspects of this manuscript.

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Correspondence to Magnus Simrén.

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Competing interests

M.S. has received unrestricted research grants from Danone and Ferring Pharmaceuticals; he has served as a consultant and/or advisory board member for Albireo, Allergan, Almirall, AstraZeneca, Danone, Glycom, Menarini, Nestlé and Shire and as a speaker for Allergan, Almirall, Menarini, Shire, Takeda and Tillotts. J.T. has given scientific advice to Almirall, AstraZeneca, Danone, Menarini, Novartis, Nycomed, Ocera, Ono pharma, Shire, SK Life Sciences, Theravance, Tranzyme, XenoPort and Zeria and has been a member of the Speaker Bureau for Abbott, Alfa Wasserman, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Nycomed, Shire and Zeria.

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Simrén, M., Tack, J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat Rev Gastroenterol Hepatol 15, 589–605 (2018). https://doi.org/10.1038/s41575-018-0034-5

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