Peer-Reviewed Journal Details
Mandatory Fields
Pruteanu, M;Hyland, NP;Clarke, DJ;Kiely, B;Shanahan, F
2011
May
Inflammatory Bowel Diseases
Degradation of the Extracellular Matrix Components by Bacterial-derived Metalloproteases: Implications for Inflammatory Bowel Diseases
Validated
WOS: 38 ()
Optional Fields
ULCERATIVE-COLITIS PATIENTS HUMAN INTESTINAL BACTERIA HUMAN MICROBIOME PROJECT CORE GUT MICROBIOME CLOSTRIDIUM-PERFRINGENS BACTEROIDES-FRAGILIS ENTEROCOCCUS-FAECALIS INNATE IMMUNITY COLONIC-MUCOSA ACTIVITY INDEX
17
1189
1200
Background: Proteolytic degradation of the extracellular matrix, a feature of mucosal homeostasis and tissue renewal, also contributes to the complications of intestinal inflammation. Whether this proteolytic activity is entirely host-derived, or, in part, produced by the gut microbiota, is unknown. Methods: We screened the bacterial colonies for gelatinolytic activity from fecal samples of 20 healthy controls, 23 patients with ulcerative colitis, and 18 with Crohn's disease (CD). In addition, the genes encoding metalloproteases were detected by conventional or real-time polymerase chain reaction (PCR). Results: Gelatinolytic activity was found in approximately one-quarter of samples regardless of the presence of inflammation and without any attempt to enhance the sensitivity of the culture-based screen. This was associated with a diversity of bacteria, particularly in CD, but was predominantly linked with Clostridium perfringens. Culture supernatants from C. perfringens degraded gelatin, azocoll, type I collagen, and basement membrane type IV collagen, but different isolates varied in the degree of proteolytic activity. Results were confirmed by detection of the C. perfringens colA gene (encoding collagenase) in fecal DNA, again regardless of the presence or absence of inflammation. However, the biologic significance and potential implications of microbial-derived proteolytic activity were confirmed by reduced transepithelial resistance (TER) after exposure of rat distal colon to culture supernatants of C. perfringens in Ussing chambers. Conclusions: The study shows that microbial-derived proteolytic activity has the capacity to contribute to mucosal homeostasis and may participate in the pathogenesis of inflammatory bowel disease. (Inflamm Bowel Dis 2011;17:1189-1200)
PHILADELPHIA
1078-0998
10.1002/ibd.21475
Grant Details