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We employed a multi-omics approach\u2014integrating transcriptomics, 16S rRNA sequencing, and serum metabolomics\u2014in a mouse model to investigate these mechanisms. Oral exposure to DON (2\u2009mg\/kg\/day for 2 weeks) induced testicular damage and disrupted the blood\u2013testis barrier, marked by the downregulation of Occludin and GJA1, alongside the suppression of steroidogenesis-related genes and proteins, including StAR and CYP17A1. Concurrently, DON triggered gut microbiota dysbiosis, characterized by an increased abundance of Desulfovibrio and a decline in beneficial bacteria. Serum metabolomics further identified a significant depletion of key fatty acids and the cholesterol precursor 5-Alpha-Cholestanol. Crucially, fecal microbiota transplantation from DON-treated mice reproduced testicular damage and suppressed steroidogenesis in recipient animals, directly establishing the causal role of gut microbiota in DON-induced reproductive toxicity. These findings collectively demonstrate that DON impairs male reproductive function by inducing gut microbiota dysbiosis and associated metabolic alterations. This work advances our understanding of the gut\u2013testis axis in toxicology and provides mechanistic insights for mitigating mycotoxin-induced reproductive dysfunction.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf155","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T01:36:53Z","timestamp":1762652213000},"source":"Crossref","is-referenced-by-count":0,"title":["Deoxynivalenol disrupts male mice reproduction through gut\u2013testis axis dysregulation and metabolic alterations"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1338-7953","authenticated-orcid":false,"given":"Pei-Yu","family":"Dong","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Qingdao Agricultural University , Qingdao 266100,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Qingdao 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