Jin Tong, Li Si-Yuan, Zheng Hong-Li, Liu Xiao-Dan, Huang Yue, Ma Gan, Zhao Ya-Xuan, Zhao Xiao-Tian, Yang Li, Wang Qi-Hui, Wang Hong-Jun, Gu Chengyong, Pan Zhiqiang, Lin Fuqing
Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China.
Department of Pain, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Gut Microbes. 2025 Dec;17(1):2495859. doi: 10.1080/19490976.2025.2495859. Epub 2025 Apr 27.
The gut microbiota has been linked to a number of neurological disorders. However, it is unclear whether the gut microbiota is involved in the genesis of chronic itch, a refractory condition that afflicts patients both physically and mentally. Here, we report that depletion of gut microbiota enhances tolerance to itch in mice orally administered with antibiotics (ABX) and mice free of germ. Of note, oral gavage with (), a prominent species of the genus with most differential change, corrected the ABX-induced itch dysfunction through its driven metabolite acetyl-l-carnitine (ALC). Mechanistically, gut microbiota or depletion caused a decrease in RNA N6-methyladenosine (mA) demethylase FTO expression in the dorsal horn and a consequent increase in RNA mA sites in Mas-related G protein-coupled receptor F () mRNA, leading to decreased MRGPRF protein. The downregulation of FTO was triggered by inactivation of ETS proto-oncogene 1 (ETS1), a transcription factor that binds to the promoter. These findings support a gut microbe - spinal connection in modulation of itch sensation in RNA mA epigenetic-dependent manner and highlight a critical role of ALC in linking the altered and itch dysfunction.
肠道微生物群已与多种神经系统疾病相关联。然而，尚不清楚肠道微生物群是否参与慢性瘙痒的发生，慢性瘙痒是一种使患者身心都备受折磨的难治性疾病。在此，我们报告称，肠道微生物群的耗竭增强了口服抗生素（ABX）的小鼠和无菌小鼠对瘙痒的耐受性。值得注意的是，用[具体物种名称未给出]（[属名未给出]中变化最显著的一个突出物种）进行口服灌胃，通过其驱动的代谢物乙酰-L-肉碱（ALC）纠正了ABX诱导的瘙痒功能障碍。从机制上讲，肠道微生物群耗竭或[具体物种名称未给出]耗竭导致背角中RNA N6-甲基腺苷（m⁶A）去甲基化酶FTO表达降低，进而导致与Mas相关的G蛋白偶联受体F（MRGPRF）mRNA中RNA m⁶A位点增加，导致MRGPRF蛋白减少。FTO的下调是由ETS原癌基因1（ETS1）失活触发的，ETS1是一种与[FTO基因名称未给出]启动子结合的转录因子。这些发现支持了肠道微生物-脊髓在以RNA m⁶A表观遗传依赖方式调节瘙痒感觉中的联系，并突出了ALC在连接改变的[具体物种名称未给出]和瘙痒功能障碍中的关键作用。
