Introduction: Our recent study demonstrated that in the absence of increased inflammatory markers in the stool, elevated fecal serine-protease activity could differentiate between patients with diarrhea predominant IBS (IBS-D) and subjects with ulcerative colitis (UC), therefore could have a diagnostic potential in IBS-D. Other proteases, the matrix metalloproteases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease, thus fecal MMP levels could also have theoretical benefit in the differenzial diagnosis of diarrhea.
Aims: The aims of this work were (i) to determine the level of MMPs (MMP 1, 2 and 9) in fecal samples from healthy controls, IBS-D and UC patients (pts), and pts with infectious diarrhea (INF), and (ii) to establish characteristic discriminative profile.
Methods: Fecal samples of healthy subjects (n=10), IBS-D (n=21), UC (n=18) and INF pts (n=12) were analyzed. MMP-1 was measured by fluorometric assay, while MMP-2, MMP-9 by ELISA.
Results: MMP-1 (11.1±3.2 vs. 3.9±0.7ng/mg protein) and MMP-2 (275.2±96.1 vs. 49.7±31.2) activities were significantly elevated in fecal supernatants of INF pts compared to healthy subjects (P<0.05). In contrast, no significant increase of MMP-1 and MMP-2 activities were found either in UC (5.0±0.7; 38.6±20.5, respectively) or in IBS-D pts (6.6±0.4; 16.4±10.2, respectively) in comparison with healthy subjects (P>0.05). MMP-9 was present in fecal supernatants from UC (4.2±2.6) and INF pts (8.8±5.8), while none of the samples from healthy subjects and IBS-D pts had any detectable expression of MMP-9.
Conclusions: While all fecal metalloproteases investigated are increased in infectious diarrhea, only MMP-9 is elevated in UC and none of them are significantly heightened in IBS-D. In diarrheic pts, the panel of fecal metalloproteases investigated exhibits a distinct profile depending on the nature of the disease underlining the interest of such biomarker screening in the assessment of the diagnosis.
