Comparative Genomic and Functional Profiling of ECM-Targeting Enzymes in Bacteroides , a Key Genus of the Human Gut Microbiome

Methods: degradation assays using purified substrates. Family-specific protease inhibitors were used to confirm the major catalytic classes involved. Genomic predictions showed limited concordance with measured enzymatic activity, suggesting context-dependent regulation of ECM-degrading enzymes. Inhibitor experiments confirmed that collagen degradation is driven primarily by metalloproteases and secondarily by serine proteases across representative species. Conclusions: as a rich, yet underappreciated, source of ECMdegrading enzymes. This work underscores the need to consider microbiota as key modulators of host tissue homeostasis and potential targets for therapeutic modulation.