Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions

Abstract

IBS is one of the most common functional gastrointestinal disorders worldwide and is thought to be the result of disturbed neural function along the brain–gut axis. The mechanisms behind this disturbance are not clear, but important roles for low-grade inflammation and immunological alterations in the development of symptoms compatible with IBS have become evident. The development of long-standing gastrointestinal symptoms after infectious gastroenteritis and patients with IBD in remission frequently having functional gastrointestinal symptoms support this hypothesis. An increased innate immune activity in the intestinal mucosa and in blood is found in subpopulations of patients with IBS. Mast cells and monocytes seem to be particularly important. In addition, studies have demonstrated that IBS may be associated with an activated adaptive immune response. Increased epithelial barrier permeability and an abnormal gut flora might lead to increased activation of the intestinal immune system. Functional and anatomical evidence for abnormal neuroimmune interactions has been found in patients with IBS. The link between immune alterations and severity of gastrointestinal symptoms and the positive effect of anti-inflammatory treatments in IBS further highlight the relevance of neuroimmune interactions in this condition.

Key Points

  • The increased risk of developing IBS after an infectious gastroenteritis and functional gastrointestinal symptoms in patients with inactive IBD support involvement of low-grade inflammation and immunological alterations in the pathogenesis of IBS

  • Increased innate immune activity has been detected in the intestinal mucosa and blood of subgroups of patients with IBS; mast cells and monocytes seem to be particularly important

  • The increased number of T cells in the intestinal mucosa and altered B-cell activity and antibody production in subgroups of patients with IBS suggest a role for the adaptive immune response

  • Alterations in the gut flora seem to be present in subgroups of patients with IBS

  • Functional and anatomical evidence for abnormal neuroimmune interactions and modestly strong associations between immune system function and the severity of gastrointestinal symptoms have been found in patients with IBS

  • Proof-of-concept studies support the role of anti-inflammatory treatment options in patients with IBS

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Figure 1
Figure 2: An increase in innate immune activity in the intestinal mucosa and blood may be found in at least subpopulations of patients with IBS.
Figure 3: Tryptase-positive mast cells in the colonic mucosa.
Figure 4: Flow cytometry for different cell types in patients with IBS.
Figure 5: Increased mast-cell infiltration in close proximity to nerve fibers in the colonic mucosa.

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Correspondence to Magnus Simrén.

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M. Simrén has served as an Advisory Board Member for Albireo, AstraZeneca, Movetis NV and Novartis and has received research funding from AstraZeneca and Danone. L. Öhman declares no competing interests.

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Öhman, L., Simrén, M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 7, 163–173 (2010). https://doi.org/10.1038/nrgastro.2010.4

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