Abstract：
Orchitis is a frequent inflammatory reproductive disease that causes male infertility and a decline in sperm quality. Gut microbiota can regulate systemic and local inflammation, spermatogenesis and blood-testosterone barrier (BTB). In this study, we investigated correlation between gut microbiota and orchitis by establishing a mouse gut microbiota imbalance model induced by antibiotics (ABX) treatment and orchitis model induced by lipopolysaccharide (LPS) infection. Based on these two models, 16s rRNA sequencing and feces microbiota transplantation (FMT) experiments were combined to examine the function and regulatory mechanisms of the gut microbiota in host defense against orchitis. Compared with control mice, gut microbiota imbalance resulted in increasing inflammatory responses, modulating oxidative stress related enzyme activity, testosterone levels and the permeability of blood testosterone barrier, which are restored after FMT. Subsequently, we tested the relationship between the gut microbiota imbalance and testicular inflammation severity in orchitis. It was found that the ABX and LPS co-treated mice had more severe inflammatory responses, lower testosterone levels and greater permeability of the BTB than the LPS-treated mice, but these changes could be partially recovered by gut microbiota transplantation. In conclusion, these above results proved for the first time that gut microbiota is involved in the pathogenesis of orchitis, which laid a good foundation for the subsequent development of anti-orchitis drugs and probiotic targeting intestinal flora.
摘要：
睾丸炎是一种常见的炎症性生殖疾病，可导致男性不育和精子质量下降。肠道菌群可以调节全身和局部炎症，精子发生和血睾酮屏障（BTB）。在这项研究中,通过建立抗生素(ABX)诱导的小鼠肠道菌群失衡模型和脂多糖(LPS)感染诱导的睾丸炎模型,探讨肠道菌群与睾丸炎的相关性.基于这两个模型，将16srRNA测序和粪便微生物群移植（FMT）实验相结合，以检查肠道微生物群在宿主防御睾丸炎中的功能和调节机制。与对照小鼠相比，肠道微生物群失衡导致炎症反应增加，调节氧化应激相关酶活性，睾酮水平和血液睾酮屏障的通透性，FMT后恢复。随后，我们测试了肠道菌群失衡与睾丸炎睾丸炎症严重程度之间的关系.发现ABX和LPS共同治疗的小鼠具有更严重的炎症反应，与LPS处理的小鼠相比，BTB的睾酮水平更低，通透性更高，但是这些变化可以通过肠道微生物移植部分恢复。总之,上述结果首次证明肠道菌群参与了睾丸炎的发病机制，为后续开发抗睾丸炎药物和针对肠道菌群的益生菌奠定了良好的基础。
