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Paradoxically, irritable bowel syndrome (IBS), a leading reason for medical consultation, is presently lacking sensitive and specific biological markers, and hence its diagnosis still relies on clinical symptom-based criteria. Luckily, and in close liaison with the progressive advent of innovative and ultrasensitive technologies and their rapid incorporation into research protocols, our mechanistic understanding of the origin of IBS may be undergoing a giant leap forward. One such remarkable advance could be the identification of a pathophysiological substrate common to the intestine of some patients with IBS—that is, a combined process of low-grade mucosal inflammation and immune activation, and disruption of the epithelial barrier.1–4 Physical and functional disintegrity of the intestinal barrier, reflected by distorted expression patterns of key selective transporters and structural proteins, and enhanced permeability, also characterises a number of inflammatory conditions including coeliac disease, inflammatory bowel disease, food allergy or type 1 diabetes, suggesting a role in disease pathogenesis.5 As for IBS, this may also be clinically relevant because the grade of barrier dysfunction has been related to the onset and severity of abdominal pain and visceral hypersensitivity.6 Interestingly, the above observations, although not unique to patients with diarrhoea-predominant IBS (d-IBS), tend to predominate in this IBS subtype.
MicroRNAs (miRNAs) are 18–25 nucleotide long RNAs serving as master endogenous fine-tuners of gene expression commonly operating via partial binding complementarity to target mRNAs. Indeed, the stability and functional expression of at least 30% of all protein-coding human genes are governed by miRNAs, acting primarily but not exclusively at the post-transcriptional level.7 In humans, the low grade repression induced by miRNAs, rarely exceeding twofold,8 mainly affects protein translation and infrequently causes degradation or cleavage of the cognate mRNA. In mammals, miRNAs comprise 2–3% of genes, found spread throughout the genome, with the exception of the …
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