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Novel insight in diarrhoea-predominant IBS: miRNAs modulate barrier function
  1. Mira M Wouters
  1. Correspondence to Dr Mira M Wouters, Translational Research Center for Gastrointestinal Disorders (TARGID), Center of Neuro-Immune Interaction and Mucosal Immunology, KU Leuven, University Hospital of Leuven, Herestraat 49, Leuven 3000, Belgium; mira.wouters{at}med.kuleuven.be

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IBS is a functional GI disorder characterised by abdominal bloating, increased visceral pain perception and an altered defaecation pattern in the absence of an organic cause. The underlying pathophysiological mechanisms that lead to abdominal pain and chronic symptoms in IBS are not fully understood. A common finding is the presence of increased mucosal intestinal permeability and an altered distribution of cell-to-cell adhesion proteins in the intestinal epithelium.1 In particular, patients with diarrhoea-predominant IBS (IBS-D)2 suffer from increased permeability, and this increase correlates with aberrant visceral sensitivity.3 Based on these observations, it is currently hypothesised that impairment of the intestinal barrier integrity facilitates the entrance of food or microbial antigens into the intestinal mucosa, thereby stimulating the mucosal immune system. Accordingly, subsets of patients with IBS show higher numbers and an increased activation of mucosal immunocytes, particularly mast cells. Bioactive mediators released by these cells, including proteases, histamine and prostanoids, participate in the perpetuation of the permeability dysfunction4 and contribute to the activation and sensitisation of (sensory) neurons5 leading to aberrant abdominal pain perception and changes in bowel habits.

Both endogenous (genetic) and environmental factors can lead to intestinal barrier impairment, but psychological stress and infectious gastroenteritis are probably the best known and strongest triggers. Increased colonic paracellular permeability has indeed been extensively observed in both chronic and acute stress murine models,6 and the connection between stress and permeability is slowly evolving in humans.7 On the other hand, infectious gastroenteritis is a common trigger for IBS, as the risk of developing IBS after acute gastroenteritis is sixfold greater than that …

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