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Pathophysiology of irritable bowel syndrome
Gerald J Holtmann1, Alexander C Ford2, Nicholas J Talley3
1Department of Gastroenterology and Hepatology, Princess Alexandra Hospital Brisbane, and Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
The Lancet. Gastroenterology & Hepatology
|April 14, 2017
Summary
Irritable bowel syndrome (IBS) may not be an unexplained brain-gut disorder. Emerging evidence suggests primary gut disturbances, including genetic factors and microbiota changes, could underlie IBS in many patients.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Immunology
Background:
- Irritable bowel syndrome (IBS) has historically been viewed as a functional disorder with no clear structural or biochemical basis.
- This perspective is challenged by recent findings suggesting underlying pathophysiological mechanisms.
- The traditional brain-gut disorder model may be incomplete or inaccurate for a significant subset of IBS patients.
Purpose of the Study:
- To review and challenge the concept of IBS as solely an unexplained brain-gut disorder.
- To explore potential primary gastrointestinal mechanisms contributing to IBS.
- To advocate for a pathophysiology-based approach to IBS treatment.
Main Methods:
- Review of epidemiological evidence linking gastrointestinal symptoms to subsequent mood disorders.
- Identification and discussion of potential underlying mechanisms for gut-brain dysfunction in IBS.
- Analysis of genetic, infectious, inflammatory, metabolic, and neurological factors implicated in IBS.
Main Results:
- Epidemiological data suggest gastrointestinal symptoms may precede mood disorders in a major subset of IBS patients.
- Identified potential mechanisms include genetic factors (e.g., SCN5A mutation), post-infectious changes, microbiota disturbances, low-grade inflammation, altered permeability, bile acid metabolism issues, and serotonin abnormalities.
- The heterogeneity of IBS symptoms likely stems from diverse underlying disease processes, not just subtypes like diarrhea-predominant or constipation-predominant.
Conclusions:
- The concept of IBS as an unexplained brain-gut disorder is likely outdated.
- Primary gut disturbances are potential underlying causes for a subgroup of IBS patients.
- A shift towards a pathophysiology-driven approach is crucial for developing targeted therapies and potentially curing IBS.