Elemental sulfur upregulated testicular testosterone biosynthesis by associating with altered gut microbiota in mice

Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years.In the present study,mice were received sulfur or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight.Then,the serum testosterone level and genes associated with testicular testosterone biosynthesis(TTB)were detected.The gut microbiota was also analyzed by 16S rRNA gene sequencing.Serum testosterone level was significantly increased by 291.1%in sulfur-treated mice.The H2S levels in serum and feces were significantly increased.The expression of genes associated with TTB including StAR,p450c17,3β-HSD,and P450scc in testes were significantly upregulated by Sulfur and NaHS,suggesting that sulfur promotes TTB depending on H2S.In addition,sulfur increased the diversity of gut microbiota and the abundance of several bacteria associated with sulfur metabolism,including genus Prevotella,which might be positively associated with serum level of testosterone in boys.Five pathways including bile secretion,carotenoid biosynthesis,lipid biosynthesis proteins,propanoate metabolism,and biosynthesis of type II polyketide products,were identified to associate with sulfur.Together,our results suggested that sulfur upregulated testicular testosterone biosynthesis via H2S,which was associated with alteration of gut microbiota in mice.Our study highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur.