Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that is characterized by abdominal pain and an altered defecation pattern. It affects between 5 and 20% of the general population and can seriously impact quality of life. The pathophysiology of IBS is rather complex and multifactorial including, for example, altered signalling by the gut–brain axis, dysbiosis, abnormal visceral pain signalling and intestinal immune activation. The latter has gained particular interest in recent years, with growing insight into the bidirectional communication between the nervous system and the immune system. In this Review, we detail the current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS and discuss the potential mechanisms involved. Moreover, we describe how immune mediators, particularly those released by mast cells, can directly activate or sensitize pain-transmitting nerves, leading to increased pain signalling and abdominal pain. Finally, we discuss the potential of interventions targeting immune activation as a new therapeutic strategy for patients suffering from IBS.
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J.A.-L. is supported by a FWO postdoctoral fellowship (12X9820N). G.E.B. is funded by the European Research Council (ERC) Advanced Grant (833816-NEUMACS) and the KU Leuven internal funding grant C1 (C14/18/086).
The authors declare no competing interests.
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Aguilera-Lizarraga, J., Hussein, H. & Boeckxstaens, G.E. Immune activation in irritable bowel syndrome: what is the evidence?. Nat Rev Immunol (2022). https://doi.org/10.1038/s41577-022-00700-9