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Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology\/immunofluorescent analysis. Primary\u2010cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in\u00a0vitro calcium imaging\/in vivo miniature two\u2010photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in\u00a0vitro, attenuated the hyper\u2010excitability in sensory neurons in MC903\u2010induced AD model, and inhibited capsaicin\u2010evoked hTRPV1 currents (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u200920.08\u2009\u00b1\u20091.11\u2009\u03bcM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene\u2010related peptide by nerves in MC903\u2010induced AD mouse model, which further attenuated itch and skin inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.15998","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T09:14:09Z","timestamp":1704186849000},"page":"1271-1290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Propionate alleviates itch in murine models of atopic dermatitis by modulating sensory\n                    <scp>TRP<\/scp>\n                    channels of dorsal root ganglion"],"prefix":"10.1111","volume":"79","author":[{"given":"Yao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoqiong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoying","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangshang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Institute of Intelligence Science and Technology  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-4775","authenticated-orcid":false,"given":"Xu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for skin diseases Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai 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