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However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host\u2019s testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of\n              <jats:italic>Akkermansia<\/jats:italic>\n              , leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host\u2019s sex hormone levels by gut microbiota.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>This study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host\u2019s testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msystems.00138-24","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T14:00:37Z","timestamp":1710252037000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of inosine metabolism of the gut microbiota decreases testosterone secretion in the testis"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3956-1437","authenticated-orcid":false,"given":"Lei","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, 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