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However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight\/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial \u03b1-diversity and Firmicutes\/Bacteroidetes ratio were drastically decreased in the captivity group. Bacteroidetes and Muribaculaceae abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites\u2019 short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between Gastranaerophilales family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.<\/jats:p>","DOI":"10.3390\/biom14040403","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:34:58Z","timestamp":1711452898000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dysbiosis of Gut Microbiome Aggravated Male Infertility in Captivity of Plateau Pika"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-2378","authenticated-orcid":false,"given":"Liangzhi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2133-0717","authenticated-orcid":false,"given":"Xianjiang","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-3922","authenticated-orcid":false,"given":"Chao","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2019en","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7853-7110","authenticated-orcid":false,"given":"Huakun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Restoration Ecology of Cold Area in Qinghai Province, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Liu","sequence":"additional","affiliation":[{"name":"Qinghai Provincial Grassland Station, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3306-7637","authenticated-orcid":false,"given":"Shangang","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Grassland Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1523-1739.2012.01829.x","article-title":"Conservation and the microbiome","volume":"26","author":"Redford","year":"2012","journal-title":"Conserv. 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