An oral–gut microbial metabolite links <i>Fusobacterium nucleatum</i> to aggravated myocardial ischemia–reperfusion injury

BACKGROUND: ), an oral pathobiont associated with cardiometabolic disease, may influence host physiology by reshaping gut microbial function through an oral-gut axis. Whether such microbial interactions contribute to MIRI remains unclear. METHODS: . Plasma metabolites, cardiac injury, ultrastructure, and p62/mTOR signaling were assessed. RESULTS: abundance, and was associated with elevated circulating ImP. Antibiotic-mediated microbiota depletion reduced ImP and attenuated myocardial injury. Plasma ImP was elevated in patients with CHD, and ImP-producing capacity was supported primarily by gut microbiota urocanate reductase (UAR)-associated functions. In H9c2 cells, ImP exacerbated hypoxia/reoxygenation injury, and increased the autophagy adaptor p62 together with downstream mTOR/S6K1 signaling. p62 knockdown attenuated the mTOR/S6K1 response and injury-associated changes, whereas IRS1 suppression persisted. CONCLUSIONS: reshapes gut microbial metabolism, thereby amplifying MIRI via ImP. ImP emerges as a functional mediator linking oral dysbiosis to MIRI, and reducing microbiota-derived ImP may represent a more mechanistically grounded strategy to mitigate MIRI.