Gut microbes-spinal connection is required for itch sensation.

Apr 28, 2025

Experts: Tong Jin,Si-Yuan Li,Hong-Li Zheng,Xiao-Dan Liu,Yue Huang,Gan Ma,Ya-Xuan Zhao,Xiao-Tian Zhao,Li Yang,Qi-Hui Wang,Hong-Jun Wang,Chengyong Gu,Zhiqiang Pan,Fuqing Lin

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.

Author

admin

View all posts

ABOUT THE EXPERTS

Tong Jin,Si-Yuan Li,Hong-Li Zheng,Xiao-Dan Liu,Yue Huang,Gan Ma,Ya-Xuan Zhao,Xiao-Tian Zhao,Li Yang,Qi-Hui Wang,Hong-Jun Wang,Chengyong Gu,Zhiqiang Pan,Fuqing Lin

Tong Jin

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.

Si-Yuan Li

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.

Hong-Li Zheng

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.

Anesthesiology Department, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.

Xiao-Dan Liu

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 Anesthesiology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.

Yue Huang

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.

Gan Ma

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.

Ya-Xuan Zhao

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.

Xiao-Tian Zhao

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.

Li Yang

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.

Qi-Hui Wang

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.

Hong-Jun Wang

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.

Chengyong Gu

Anesthesiology Department, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.

Zhiqiang Pan

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.

Fuqing Lin

Department of Pain, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China.