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Original Article
Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
  1. Jan Tack1,
  2. Maura Corsetti2,
  3. Michael Camilleri3,
  4. Eamonn MM Quigley4,
  5. Magnus Simren5,
  6. Hidekazu Suzuki6,
  7. Nicholas J Talley7,
  8. Hans Tornblom5,
  9. Lukas Van Oudenhove1
  1. 1Translational Research Center for Gastrointestinal Disorders, KULeuven, Leuven, Belgium
  2. 2Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
  3. 3CENTER Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  4. 4Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA
  5. 5Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  6. 6Gastroenterology, Keio University, Tokyo, Japan
  7. 7Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia
  1. Correspondence to Prof Jan Tack, University of Leuven Herestraat 49, box 701 3000 Leuven, Belgium ; jan.tack{at}med.kuleuven.be

Abstract

Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances.

Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs.

Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism.

Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

  • Functional Dyspepsia
  • Functional Bowel Disorder
  • Gastric Motility
  • Non-cardiac Chest Pain
  • Irritable Bowel Syndrome

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Footnotes

  • Contributors All authors equally contributed to the concept, content, manuscript writing and manuscript revision.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The affiliations for the second and third authors have been updated.

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