2. Academic Validation
  3. Identification of Critical Gut Metabolites Mediating the Protective Effects of Lacticaseibacillus paracasei on Myocardial Injury in Mice

Identification of Critical Gut Metabolites Mediating the Protective Effects of Lacticaseibacillus paracasei on Myocardial Injury in Mice

  • J Agric Food Chem. 2025 Jul 30;73(30):18822-18840. doi: 10.1021/acs.jafc.5c08360.
Xiaolin Wu 1,  Jing Yang 2,  Jiayang Liao 1,  Zsolt Zalán 3,  Jianquan Kan 1 4,  Huayi Suo 1 4,  Yu Zhang 1,  Jiajia Song 1 4
Affiliations

Affiliations

  • 1 College of Food Science, Southwest University, Chongqing 400715, P. R. China.
  • 2 School of Food Science and Engineering, Chongqing Technology and Business University, Chongqing 400067, P. R. China.
  • 3 Food Science and Technology Institute, Hungarian University of Agriculture and Life Sciences, Buda Campus, Herman Ottó Street 15, Budapest 1022, Hungary.
  • 4 Chinese-Hungarian Cooperative Research Centre for Food Science, Chongqing 400715, P. R. China.
PMID: 40680093 DOI: 10.1021/acs.jafc.5c08360
Abstract

Heart failure is a leading cause of mortality worldwide, with myocardial injury as a major pathological contributor. Probiotics have shown cardioprotective effects, but their key gut metabolites remain unclear. In this study, Lacticaseibacillus paracasei DACN528, isolated from traditional fermented yak yogurt, significantly improved body weight (13.95% increase) and heart index (18.73% increase) and reduced serum cTnI and NT-proBNP levels by 54.96 and 22.05%, respectively, in a doxorubicin-induced mouse model of myocardial injury (all p < 0.05). Electrocardiographic abnormalities were attenuated, including reductions in QT interval (29.13%), PR interval (7.98%), and ST segment elevation (28.74%). Histological analyses revealed reduced myocardial fibrosis and Apoptosis, with regulation of fibrosis- and apoptosis-related genes. DACN528 also modulated mitochondrial dynamics and Autophagy by altering expression of Fis1, Drp1, Mfn2, and Parkin. Moreover, it reshaped gut microbiota composition by increasing beneficial taxa such as Lactobacillus and norank_f__Muribaculaceae while decreasing harmful ones such as Allobaculum. Metabolomic and correlation analyses identified seven microbial metabolites potentially involved in cardioprotection. Among them, 5-hydroxymethylfurfural showed protective effects in H9C2 cardiomyocytes. These findings provide mechanistic insights into probiotic-mediated myocardial protection and support DACN528 as a promising candidate for cardiovascular health interventions.

Keywords

Lacticaseibacillus paracasei; gut microbiota metabolites; mitochondrial homeostasis; myocardial injury.

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