Understanding the Role of Gut Microbial Enzyme in CMD

Cardiometabolic diseases (CMDs) refer to a broad spectrum of interconnected disorders, including heart attack, obesity, diabetes, atherosclerosis, and metabolic dysfunction-associated steatohepatitis, which represent the leading cause of mortality worldwide. In recent years, research on the role of gut microbiota in the pathogenesis of CMD has gradually shifted from correlation-based observations to mechanistic explorations. Within this context, microbial enzymes have gained increasing attention as key regulatory factors. These enzymes not only participate in the metabolic regulation of microorganisms themselves but also directly mediate host-microbe interactions, influencing the onset and progression of CMD. Specifically, microbial enzymes play a central role in CMD by modulating the homeostasis of key host metabolites such as cholesterol, generating bioactive molecules with metabolic and immunoregulatory functions, and participating in drug responses and the metabolic transformation of other xenobiotics. These enzymes provide novel and well-defined molecular targets for developing precision intervention strategies targeting the gut microbiota-such as enzyme replacement therapy, the design of enzyme agonists or inhibitors, and in vivo gene editing-thereby holding promise for advancing CMD prevention and treatment strategies toward greater specificity and controllability. This review systematically summarizes key microbial enzymes involved in the metabolism of endobiotics, including amino acids, peptides, and purines, and xenobiotics such as drugs, elucidating their specific mechanisms and functions in the development of CMD, strategies for mining these microbial enzymes, and the challenges and future of microbial enzyme-based interventions.