Lactiplantibacillus plantarum P133, a Folate-Producing Probiotic, Ameliorates Cardiac Injury in Hyperhomocysteinemia Mice by Modulating Gut Microbiota and Serum Metabolome

Hyperhomocysteinemia (HHcy) constitutes a significant risk factor for cardiovascular disease. The present study examined the cardioprotective effects and underlying mechanisms of the folate-producing strain Lactiplantibacillus plantarum (L. plantarum) P133, isolated from traditional fermented pickled vegetables, in a murine model of HHcy induced by a methionine-choline-deficient diet. The findings revealed that administration of P133 significantly reduced serum homocysteine concentrations and improved cardiac function, as evidenced by decreased serum cardiac enzymes (AST, LDH, Ctnt, Ctni), mitigated myocardial histopathological damage, and lowered oxidative stress levels (e.g., decreased MDA). Mechanistically, P133 appears to provide dual protective effects: firstly, it functions as an intrinsic source of folate, thereby mitigating disturbances in one-carbon metabolism; secondly, it influences the composition of the gut microbiota, significantly enhancing the prevalence of beneficial taxa such as Muribaculaceae, and modifies the serum metabolomic profile by increasing favorable metabolites like indoleacetic acid, which correlate strongly with attenuated cardiac injury. These synergistic effects are associated with attenuated cardiac injury. Therefore, L. plantarum P133 emerges as a promising probiotic candidate for the prevention and treatment of cardiac damage related to HHcy via a multifaceted intervention approach.