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We read with great interest the article by Matricon et al.,[1] who performed an exhaustive literature review to identify the potential roles of intestinal immunity and gut permeability in irritable bowel syndrome (IBS). Although the results were often found to be heterogeneous as concerning methods, markers and patients included, they open new perspectives in understanding mechanisms underlying such intestinal dysfunction.

Clear inflammation such as found in IBD[2] is lacking in IBS, but a state of heightened immune activation, which underlies an ongoing low-grade inflammatory response, seems to be present, particularly in the post-infectious IBS subtype. Evidence for this is multifaceted.[3] There are greater numbers of mucosal-type mast-cells, T-type and intraepithelial lymphocytes with altered tryptase, histamine and cytokine production from innate-immunity cells in the gut of IBS patients than in healthy controls. However, other inflammatory indicators, such as B-lymphocytes and enterocromaffin cells or faecal lactoferrin and calprotectin levels, are not different. Furthermore, a higher intestinal permeability and a lower number of tight junction proteins are found in the intestinal epithelium of IBS patients than in healthy controls.[4]

The Authors point out that non-inflammatory factors are involved in IBS aetiology, particularly in the Diarrhoea-IBS, Constipation-IBS and Alternating-IBS subtypes. Depression and stress are two major factors,[5] which may induce sensory-motor alteration in the gut, such as visceral hypersensitivity, and alter the production of cytokines, thus influencing the immune system. Whether inflammation is a cause or a consequence of IBS remains to be clarified.[6]

The authors conclude that alteration of the immune system, together with alteration of the integrity of the epithelial barrier, is associated with IBS, but the role of brain–gut axis in this scheme needs further investigation.

It has been suggested that alteration of the gut microbiome[7] and small intestinal bacterial overgrowth (SIBO)[8] may also play a role in the aetiopathogenesis of IBS. The benefits of probiotics[9] and rifaximin[10] treatment in IBS support such an hypothesis. We believe, this may too be a productive area of future research in the aetiopathogenesis and cure of IBS.

Acknowledgement

  1. Top of page
  2. Acknowledgement
  3. References

Declaration of personal interests: S. Danese has served as a consultant for Alfa Wasserman. Declaration of funding interests: None.

References

  1. Top of page
  2. Acknowledgement
  3. References
  • 1
    Matricon J, Meleine M, Gelot A, et al. Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 2012; 36: 100931.
  • 2
    Van Assche G, Dignass A, Panes J, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. J Crohns Colitis 2010; 4: 727.
  • 3
    Barbara G, Cremon C, Carini G, et al. The immune system in irritable bowel syndrome. J Neurogastroenterol Motil 2011; 17: 34959.
  • 4
    Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2012; 303: G77585.
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    Sinagra E, Romano C, Cottone M. Psychopharmacological treatment and psychological interventions in irritable bowel syndrome. Gastroenterol Res Pract 2012; 2012: 486067.
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    Kim SE, Chang L. Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms? Neurogastroenterol Motil 2012; 24: 895913.
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    Chassard C, Dapoigny M, Scott KP, et al. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther 2012; 35: 82838.
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    Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci 2012; 57: 13219.
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    Balakrishnan M, Floch MH. Prebiotics, probiotics and digestive health. Curr Opin Clin Nutr Metab Care 2012; 15: 5805.
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    Cremonini F, Lembo A. Rifaximin for the treatment of irritable bowel syndrome. Expert Opin Pharmacother 2012; 13: 43340.