Objective High-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility. Design Faecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin. Results Transplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice. Conclusion We revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes. Trial registration number NCT03634644.

中文翻译：

---

高脂肪饮食引起的肠道微生物失调对精子发生和精子活力的损害

目的 高脂肪饮食 (HFD) 引起的代谢紊乱会导致精子生成受损。我们旨在研究 HFD 诱导的肠道微生物群失调是否可以在功能上影响精子发生和精子活力。设计 来自 HFD 喂养或正常饮食 (ND) 喂养的雄性小鼠的粪便微生物被移植到维持在 ND 上的小鼠。分析了肠道微生物、精子数量和运动能力。收集人类粪便/精液/血液样本以评估微生物群、精子质量和内毒素。结果 将 HFD 肠道微生物移植到 ND 维持 (HFD-FMT) 小鼠中导致精子发生和精子活力显着降低，而用来自 ND 喂养小鼠的微生物进行类似移植却未能做到这一点。微生物群分析显示拟杆菌属和普氏菌属显着增加，这两者都可能导致 HFD-FMT 小鼠的代谢性内毒素血症。有趣的是，来自临床受试者的肠道微生物揭示了拟杆菌-普氏菌丰度与精子活力之间的强烈负相关，以及血液内毒素与拟杆菌丰度之间的正相关。HFD 微生物移植还导致 T 细胞和巨噬细胞的肠道浸润以及附睾中促炎细胞因子的显着增加，表明附睾炎症可能导致精子活力受损。RNA 测序显示，在 HFD-FMT 小鼠中，参与配子减数分裂和睾丸线粒体功能的那些基因的表达显着降低。结论 我们揭示了 HFD 诱导的微生物群失调与精子发生缺陷之间存在密切联系，内毒素升高、睾丸基因表达失调和局部附睾炎症是潜在原因。试验注册号 NCT03634644。