Dietary Matcha Attenuates High-Fat High-Sugar Diet-Induced Cardiomyocyte Hypertrophy in Association with Gut Microbiota Remodeling in Mice

Objectives: Obesity is associated with cardiac remodeling characterized by cardiomyocyte hypertrophy and fibrosis, eventually leading to heart failure. This study aimed to evaluate whether dietary matcha supplementation could be effective in reducing high-fat, high-sugar diet (HFD)-induced cardiac remodeling in mice, and whether this effect is linked to changes in the gut microbiota along the gut–heart axis. Methods: Six-week-old C57BL/6J mice were randomly divided into normal chow diet (NCD) or HFD (without matcha, 0.2% matcha, or 1% matcha) groups. Dietary intervention continued for 10 weeks with continuous monitoring of body weight. After completion of the intervention, hearts were collected, weighed, and processed for histological examination of cardiomyocyte size with wheat germ agglutinin (WGA) staining and collagen deposition with Picrosirius Red staining. The gut microbiome was evaluated using 16S rRNA sequencing of gDNA from feces, and correlation analysis was performed between microbial taxa and cardiometabolic parameters. Results: After 10 weeks of dietary intervention, heart weight was significantly lower in mice treated with 1% matcha than in HFD controls. WGA staining showed a significant increase in cardiomyocyte size in the HFD group compared with the NCD group, whereas both the 0.2% and 1% matcha-supplemented groups revealed significantly smaller cardiomyocytes than the HFD controls. In addition, both matcha doses significantly reduced cardiac collagen deposition relative to HFD controls. In the gut, matcha supplementation displayed a marked increase in the abundance of beneficial gut microbiota, including Ligilactobacillus, Lactobacillus, and Oscillospiraceae, while reducing pathogenic Enterobacteriaceae and Klebsiella, particularly at the high dose. Conclusions: Dietary matcha supplementation attenuated HFD-induced cardiac hypertrophy and fibrosis in mice, independently of body weight, in association with modulation of the gut microbiota along the gut–heart axis. Future studies should determine whether the observed reductions in cardiac hypertrophy and fibrosis translate into measurable improvements in cardiac function and whether the associated gut microbiota alterations exert causal effects on cardiac remodeling.