PT  - JOURNAL ARTICLE
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
TI  - Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes
AID  - 10.1136/gutjnl-2019-319127
DP  - 2020 Sep 01
TA  - Gut
PG  - 1608--1619
VI  - 69
IP  - 9
4099  - http://gut.bmj.com/content/69/9/1608.short
4100  - http://gut.bmj.com/content/69/9/1608.full
SO  - Gut2020 Sep 01; 69
AB  - 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.