Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Abstract

Although the etiology of irritable bowel syndrome (IBS) remains unknown, clinical and laboratory observations suggest that within the broad and varying phenotype, that is, IBS, there may exist subgroups, which can be defi ned on the basis of a distinctive pathophysiological basis. Of these, postinfectious IBS is the best characterized; in IBS, in general, studies of infl ammatory mediators and substances elaborated by cells involved in the intestinal immune response, such as proteases, suggest that some IBS sufferers can be differentiated on the basis of an aberrant immune response. Valdez-Morales and colleagues extend this concept by demonstrating the ability of supernatants of biopsy cultures from individuals with diarrheapredominant IBS to enhance neuronal excitabilityan effect that could well contribute to a clinical hallmark of IBS, namely, visceral hypersensitivity. Am J Gastroenterol 2013; 108:1644 -1646 doi: 10.1038/ajg.2013 Irritable bowel syndrome (IBS) is a common and, at times, disabling condition whose etiology, despite the best eff orts of clinicians and scientists, remains unclear. As a consequence, reliable biomarkers for the syndrome have yet to emerge, and its diagnosis, therefore, continues to rest on clinical features and the exclusion of disorders that have the potential to present in a similar manner ( 1 ). Much of the diffi culties related to unraveling the enigma that is IBS revolve around its heterogeneity, which may originate from any one or a combination of the following: dominant symptom (pain, discomfort, bloating, distension, and altered bowel habit), predominant bowel habit (diarrhea, constipation, or mixed pattern), comorbidity (be it psychological or somatic), severity (including impact on the quality of life), natural history, and prognosis. To frustrate the clinician scientist further, those IBS subtypes that can be defi ned with some degree of accuracy, at least using Rome III criteria (2), including diarrhea-predominant IBS, constipationpredominant IBS and mixed IBS, do not appear to be immutable, and suff erers can move from one stool pattern to another over time, thus emphasizing the importance of longitudinal studies of this disorder ( 3,4 ).However, in this rather gloomy scenario, shines an unexpected beam of light that has illuminated (or, to be accurate, reignited) a new perspective on the etiology of IBS -postinfectious IBS (PI-IBS) ( 5 ). Although PI-IBS had been well described decades beforehand ( 6 ), more recent studies based on the consequences of large-scale outbreaks of bacterial, viral, and amebic gastroenteritis have firmly brought the concept of host -microbiome interactions into play in IBS research, in general ( 7 ). Observations in relation to PI-IBS, such as the description of correlations between the initial inflammatory response to the infection and the subsequent development of IBS ( 8 ), as well as the identification of polymorphisms in genes coding for components of the mucosal immune response and intestinal barrier integrity as risk factor...

Molecular mechanism of Sishen pills in the treatment of diarrheal diabetic enteropathy based on network pharmacology

“…PAR is a G protein-coupled receptor involved in the functional regulation of gastrointestinal sensation, intestinal mucosal inflammation response, and gastrointestinal smooth muscle movement and plays a regulatory role in functional gastrointestinal disease. [ 36 ] PAR2 is widely distributed in the digestive tract, where it activates the PAR2 receptor of intestinal epithelial cells and stimulates the intestinal mucosa to secrete a large amount of water, which causes diarrhea. [ 37 ] PAR2 can also be involved in the regulation of intestinal function by influencing intestinal motility and increasing intestinal mucosal permeability and exhibits high sensitivity.…”