Guanxinning attenuates diabetic myocardial ischemia–reperfusion injury by targeting oral Fusobacterium nucleatum and modulating PTEN signaling

作者：Yiwen Li, Qian Xu, Yanfei Liu, Yanfei Liu, Longkun Liu, Wenting Wang, Mengmeng Zhu, Jing Cui, Hongjun Yang, Yue Liu, Yue Liu · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1581413 · 被引用次数：3 · 研究领域：Gut microbiota and health、Streptococcal Infections and Treatments、Oral microbiology and periodontitis research

Background The incidence and severity of diabetic myocardial ischemia reperfusion injury (DMIRI) are increasing, highlighting the urgent need for effective prevention and treatment. Previous studies have revealed that specific oral microbiota ( Fusobacterium nucleatum ) are closely involved in DMIRI, potentially serving as therapeutic targets. Guanxinning (GXN) has shown significant efficacy in treating diabetic cardiomyopathy. However, its mechanisms of action regarding DMIRI and its relationship with specific microbiota remain to be elucidated. Proposal This study investigates whether GXN alleviates DMIRI by modulating F. nucleatum and host interactions. Methods The effects of GXN on cardiac injury, cardiac protein expression and the abundance of F. nucleatum were evaluated in C57BL/6 mice under both conventional and germ-free conditions. GWAS analysis was employed to identify potential mechanisms linking F. nucleatum and DMIRI. Fusobacterium nucleatum IgG levels were measured, and LC-MS/MS metabolomics along with Metorigin trace-ability analysis were conducted to validate the proposed mechanisms. Results GXN treatment significantly reduced myocardial injury in diabetic mice and decreased oral F. nucleatum abundance, although its effects on other gut microbiota taxa were variable. Importantly, the cardioprotective efficacy of GXN was markedly attenuated under pseudo-germ-free conditions, suggesting that its benefits are at least partly microbiota-dependent. PI3K signaling p...