Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome.
Other proteases, namely cysteine-proteases, increase airway permeability by digesting epithelial tight junction proteins.
Dr Anita Annaházi and from France focused on constipation-predominant irritable bowel syndrome-C, and evaluated cysteine-proteases levels in 2 cohorts of irritable bowel syndrome patients.
The team tested if irritable bowel syndrome-C fecal supernatant affects permeability, and visceral sensitivity after repeated administrations in mice, and evaluated occludin expression in irritable bowel syndrome-C colonic biopsies.
Fecal constipation-predominant activity was determined using selective substrate and inhibitor.
The effect of papain, as positive control, and irritable bowel syndrome-C fecal supernatant administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice, and T84 monolayers.
|Cysteine-proteases activity levels positively correlated with abdominal pain scoring|
|American Journal of Gastroenterology|
Occludin protein levels were evaluated in irritable bowel syndrome-C colonic biopsies.
Sensitivity to colorectal distension was measured after repeated administrations of irritable bowel syndrome-C fecal supernatant.
The doctors found in a subset of IBS-C patients an enhanced fecal cysteine-proteases activity, in comparison with healthy controls and irritable bowel syndrome patients.
Cysteine-proteases activity levels positively correlated with disease severity, and abdominal pain scoring.
This association was confirmed by receiver operating characteristic curve analysis.
In mice, repeated application of irritable bowel syndrome-C fecal supernatant into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD.
The team observed occludin levels decreased in colonic biopsies from irritable bowel syndrome-C patients, and rritable bowel syndrome-C fecal supernatant were able to degrade recombinant human occludin in vitro.
All these effects were abolished by preincubation of irritable bowel syndrome-C fecal supernatant with a cysteine-protease inhibitor, E64.
Dr Annaházi's team concludes, "These data suggest that luminal cysteine-proteases may represent a new factor contributing to the genesis of symptoms in irritable bowel syndrome."