Cited by 67Inflammatory Bowel DiseaseGut microbiota and healthProtease and Inhibitor Mechanisms

Degradation of the extracellular matrix components by bacterial-derived metalloproteases: Implications for inflammatory bowel diseases

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Pruteanu, Mihaela, Hyland, Niall P., Clarke, David J., Kiely, Barry, Shanahan, Fergus·2011·Inflammatory Bowel Diseases

Abstract

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.

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Authors
Pruteanu, M., Hyland, N. P., Clarke, D. J., Kiely, B., & Shanahan, F.
Affiliations
  • National University of Ireland (IE)
  • Alimentary Health (Ireland) (IE)
Venue
Inflammatory Bowel Diseases
Published
2011-05
Volume
17
Issue
5
Pages
1189-1200
ISSN
1078-0998 (ISSN-L)
OpenAlex
W2073360547
Cited by
67
References
64
Citations by year
2025: 3 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 6 · 2019: 8 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 9
FWCI
3.41
Type
journal article
Language
en
Open access
Locations
  • Inflammatory Bowel Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Funders
  • European Commission (202020)
  • Science Foundation Ireland
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
extracellular matrix degradation
MeSH terms
Adult, Animals, Bacterial Proteins, Basement Membrane, Microbial Collagenase, Clostridium perfringens, Colitis, Ulcerative, Crohn Disease, Extracellular Matrix, Feces, Humans, Metalloendopeptidases, Microbiological Techniques, Middle Aged, Staphylococcus epidermidis, Polymerase Chain Reaction, Collagen Type IV, Gastrointestinal Tract, Metalloproteases, Rats, Metagenome, In Vitro Techniques

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