Fu Zhi-Ping, Ying Yi-Ge, Wang Rui-Yao, Wang Yu-Qing
Collage of Pharmacology, North China University of Science and Technology, Tangshan 063200, China.
iScience. 2024 Sep 4;27(10):110888. doi: 10.1016/j.isci.2024.110888. eCollection 2024 Oct 18.
Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (HO) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.
心律失常和心源性猝死（SCD）造成了重大负担。它们的患病率随年龄增长而上升，且与肠道菌群失调有关。我们的研究旨在确定老年肠道微生物群是否会影响心律失常的发生。在此，我们证明了老年小鼠的心律失常易感性可通过粪便微生物群移植（FMT）传递给年轻小鼠。从机制上讲，老年小鼠肠道活性氧（ROS）增加会降低离子通道蛋白表达并促进心律失常。用抗生素鸡尾酒清除肠道微生物群可降低老年小鼠的ROS和心律失常。有趣的是，过氧化氢（HO）诱导的心脏氧化应激会增加心律失常。此外，老年肠道微生物群可通过肠道微生物群代谢产物移植在年轻小鼠结肠中诱导氧化应激。牡荆素可通过OLA1-Nrf2信号通路减轻衰老和心律失常。总体而言，我们的研究表明，老年小鼠的肠道微生物群通过全身氧化应激降低心脏离子通道蛋白表达，从而增加心律失常的风险。
