TY - JOUR T1 - Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes JF - Gut JO - Gut DO - 10.1136/gutjnl-2019-319127 SP - gutjnl-2019-319127 AU - Ning Ding AU - Xin Zhang AU - Xue Di Zhang AU - Jun Jing AU - Shan Shan Liu AU - Yun Ping Mu AU - Li Li Peng AU - Yun Jing Yan AU - Geng Miao Xiao AU - Xin Yun Bi AU - Hao Chen AU - Fang Hong Li AU - Bing Yao AU - Allan Z Zhao Y1 - 2019/12/31 UR - http://gut.bmj.com/content/early/2020/01/02/gutjnl-2019-319127.abstract N2 - 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. ER -