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Accumulating studies suggest that gut microbiota may play a role in depression via gut\u2013microbiota\u2013brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.<\/jats:p>","DOI":"10.1038\/s41398-019-0379-8","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T12:04:03Z","timestamp":1548936243000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":161,"title":["Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain"],"prefix":"10.1038","volume":"9","author":[{"given":"Chun","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niannian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangjiang","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"379_CR1","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1001\/archinte.163.20.2433","volume":"163","author":"MJ Bair","year":"2003","unstructured":"Bair, M. 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Braun Medical Inc. The remaining authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"57"}}