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Matrix Metalloproteinases (MMPs) can be co-opted by pathogens to facilitate infection and tissue invasion.
Matrix Metalloproteinases (MMPs)
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Matrix Metalloproteinases (MPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.
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Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview Overview
Matrix Metalloproteinases (MMPs) are a family of zinc-dependent proteolytic enzymes critical for the degradation and remodeling of extracellular matrix (ECM) components. These enzymes are essential for normal physiological processes, such as wound healing, tissue remodeling, and angiogenesis. However, dysregulated MMP activity is implicated in pathological conditions, including chronic inflammation, cancer, cardiovascular diseases, and microbial dysbiosis.
Structure and Regulation
MMPs are initially synthesized as inactive zymogens (pro-MMPs) and require proteolytic activation to function. Their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), ensuring precise ECM remodeling. Factors influencing MMP activity include cytokines, growth factors, oxidative stress, and microbial metabolites. Zinc and calcium ions are critical cofactors for their catalytic activity.
Families and Specific Types of MMPs
MMPs are categorized based on substrate specificity and structure:
Collagenases (e.g., MMP-1, MMP-8): Target fibrillar collagens.
Gelatinases (e.g., MMP-2, MMP-9): Degrade collagen IV and gelatin.
Stromelysins (e.g., MMP-3, MMP-10): Act on proteoglycans, laminin, and non-collagenous proteins.
Membrane-Type MMPs (e.g., MMP-14): Localized to cell surfaces, regulating ECM in proximity to cells.
Role in Disease Pathophysiology
Matrix Metalloproteinases (MMPs) are elevated in various inflammatory and chronic diseases, including inflammatory bowel disease (IBD), periodontitis, and rheumatoid arthritis, where they contribute to extracellular matrix (ECM) breakdown and perpetuate inflammation. In gingivitis, MMPs play a critical role in tissue damage, often influenced by oral dysbiosis. In cancer, MMPs facilitate tumor invasion, angiogenesis, and metastasis through ECM degradation, with MMP-9 and MMP-14 being particularly implicated in cancer progression. Furthermore, dysregulated MMP activity is linked to neuroinflammation, blood-brain barrier disruption, and neurodegeneration in neurological disorders such as Alzheimer’s and Parkinson’s disease.
Microbiome-Specific Insights
Matrix Metalloproteinases (MMPs) can be co-opted by pathogens to facilitate infection and tissue invasion. Certain bacteria and viruses upregulate MMP activity, breaking down extracellular matrix barriers and promoting microbial dissemination. This dual role of MMPs—as essential mediators of tissue repair and potential enablers of pathogenic invasion—highlights the need for clinicians to consider MMP activity when evaluating inflammatory or infectious diseases, particularly in the context of dysbiosis or chronic inflammation.
Microbial Influence: Microbiota can modulate MMP expression and activity. For instance, lipopolysaccharides (LPS) from Gram-negative bacteria upregulate MMP-9 in inflammation.
Biofilm Dynamics: MMPs can degrade biofilm-associated ECM or may be hijacked by pathogens to facilitate invasion.
Microbial Dysbiosis and Inflammation: Altered microbial populations can exacerbate MMP overexpression, contributing to chronic diseases like periodontitis and IBD.
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.