Gut microbes–spinal connection is required for itch sensation
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 enhance...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2495859 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tong Jin |
| collection | DOAJ |
| description | 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 Bacteroides fragilis (B. fragilis), a prominent species of the genus Bacteroides with most differential change, corrected the ABX-induced itch dysfunction through its driven metabolite acetyl-l-carnitine (ALC). Mechanistically, gut microbiota or B. fragilis depletion caused a decrease in RNA N6-methyladenosine (m6A) demethylase FTO expression in the dorsal horn and a consequent increase in RNA m6A sites in Mas-related G protein-coupled receptor F (MrgprF) 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 Fto promoter. These findings support a gut microbe – spinal connection in modulation of itch sensation in RNA m6A epigenetic-dependent manner and highlight a critical role of ALC in linking the altered B. fragilis and itch dysfunction. |
| format | Article |
| id | doaj-art-0e045c73b0ed40ea819d51746335c7fd |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-0e045c73b0ed40ea819d51746335c7fd2025-08-20T02:20:05ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2495859Gut microbes–spinal connection is required for itch sensationTong Jin0Si-Yuan Li1Hong-Li Zheng2Xiao-Dan Liu3Yue Huang4Gan Ma5Ya-Xuan Zhao6Xiao-Tian Zhao7Li Yang8Qi-Hui Wang9Hong-Jun Wang10Chengyong Gu11Zhiqiang Pan12Fuqing Lin13Jiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaJiangsu 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, ChinaAnesthesiology Department, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, ChinaJiangsu 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, ChinaDepartment of Pain, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaThe 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 Bacteroides fragilis (B. fragilis), a prominent species of the genus Bacteroides with most differential change, corrected the ABX-induced itch dysfunction through its driven metabolite acetyl-l-carnitine (ALC). Mechanistically, gut microbiota or B. fragilis depletion caused a decrease in RNA N6-methyladenosine (m6A) demethylase FTO expression in the dorsal horn and a consequent increase in RNA m6A sites in Mas-related G protein-coupled receptor F (MrgprF) 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 Fto promoter. These findings support a gut microbe – spinal connection in modulation of itch sensation in RNA m6A epigenetic-dependent manner and highlight a critical role of ALC in linking the altered B. fragilis and itch dysfunction.https://www.tandfonline.com/doi/10.1080/19490976.2025.2495859Gut microbeitchFTORNA m6AB. fragilisacetyl-l-carnitine |
| spellingShingle | 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 Gut microbes–spinal connection is required for itch sensation Gut Microbes Gut microbe itch FTO RNA m6A B. fragilis acetyl-l-carnitine |
| title | Gut microbes–spinal connection is required for itch sensation |
| title_full | Gut microbes–spinal connection is required for itch sensation |
| title_fullStr | Gut microbes–spinal connection is required for itch sensation |
| title_full_unstemmed | Gut microbes–spinal connection is required for itch sensation |
| title_short | Gut microbes–spinal connection is required for itch sensation |
| title_sort | gut microbes spinal connection is required for itch sensation |
| topic | Gut microbe itch FTO RNA m6A B. fragilis acetyl-l-carnitine |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2495859 |
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