White hyacinth bean polysaccharide mitigates high-fat diet-induced myocardial injury by modulating the gut microbiota-phenylalanine-heart axis in mice

Long-term high-fat diet (HFD) was widely recognized as a critical factor for occurrence and progression of cardiovascular diseases. This study aimed to investigate whether white hyacinth bean polysaccharide (WHBP), a potential prebiotic functional food ingredient, alleviated HFD-induced myocardial injury and elucidated underlying mechanisms. Here, an obese mice model was established by 12-week HFD feeding. From the 13th week, HFD-fed mice received WHBP (25, 50 or 100 mg/kg body weight) once daily for 4 weeks. WHBP administration significantly attenuated HFD-induced cardiac histopathological injury, inflammation, oxidative stress, and elevated creatine kinase and lactate dehydrogenase levels, with the most pronounced effects observed at the higher doses. Furthermore, WHBP improved intestinal barrier integrity by upregulating ZO-1 and Claudin-1 and reshaped gut microbiota composition, including manipulating the Firmicutes/Bacteroidota ratio and enriching beneficial genera such as Akkermansia and Lactobacillus . Serum metabolomics identified phenylalanine metabolism as a bridge pathway associated with WHBP-induced microbiota remodeling. Notably, phenylalanine accumulation was also increased in cardiac tissue under HFD and was reversed by WHBP, suggesting a gut-heart crosstalk underlying HFD-induced myocardial injury. Mechanistically, WHBP reduced phenylalanine accumulation and then restored mitochondrial fatty acid oxidation by upregulating PPARα, PGC-1α, and LCAD, thereby enhancing TCA cycle activity and ATP production. Collectively, WHBP protected against HFD-induced myocardial injury via a gut microbiota-phenylalanine-heart axis, highlighted its potential as a dietary strategy for obesity-associated cardiac dysfunction.