Ioannou Paraskevi, Katsoulieris Elias, Afratis Nikolaos A
Laboratory of Biotechnology and Molecular Analysis, Department of Agricultural Development, Agri-Food & Management of Natural Resources, National and Kapodistrian University of Athens, Evripos Campus, 34400 Psachna, Evia, Greece.
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot 7610001, Israel.
Int J Mol Sci. 2025 Apr 11;26(8):3621. doi: 10.3390/ijms26083621.
Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix (ECM) remodeling, regulating a wide range of cellular and immune processes in both homeostatic and pathological conditions. Host-microbiota interactions play a critical role in maintaining ECM balance; however, during dysbiosis, this regulation is disrupted, leading to compromised barrier integrity, pathogen translocation into circulation, and the development of systemic diseases and cancer. This review highlights the bidirectional relationship between MMP expression/activity and microbiota dysbiosis, emphasizing tissue-specific alterations in MMP activity that contribute to disease progression. In addition, it integrates interdisciplinary evidence to illustrate the MMP-dependent mechanisms underlying various pathologies associated with oral and gut microbiome dysbiosis, including long-range effects through the gut-skin and gut-brain axes. Thus, this review introduces the emerging field of , which explores the complex interactions between the ECM, microbiota, and host tissues. Finally, it also outlines therapeutic strategies to modulate MMP levels, either indirectly through microbiome-targeted approaches (, prebiotics, probiotics, and postbiotics) or directly using MMP inhibitors, offering promising avenues for future clinical interventions.
基质金属蛋白酶（MMPs）是参与细胞外基质（ECM）重塑的关键酶，在稳态和病理条件下调节广泛的细胞和免疫过程。宿主-微生物群相互作用在维持ECM平衡中起关键作用；然而，在生态失调期间，这种调节被破坏，导致屏障完整性受损、病原体易位进入循环以及全身性疾病和癌症的发生。本综述强调了MMP表达/活性与微生物群生态失调之间的双向关系，强调了MMP活性的组织特异性改变对疾病进展的影响。此外，它整合了跨学科证据，以阐明与口腔和肠道微生物群生态失调相关的各种病理背后的MMP依赖性机制，包括通过肠-皮肤和肠-脑轴的远程效应。因此，本综述介绍了新兴的 领域，该领域探索ECM、微生物群和宿主组织之间的复杂相互作用。最后，它还概述了调节MMP水平的治疗策略，要么通过针对微生物群的方法（如益生元、益生菌和后生元）间接调节，要么直接使用MMP抑制剂，为未来的临床干预提供了有希望的途径。
