Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

• Published in: Gut Vol. 69; no. 9; pp. 1608 - 1619
• Main Authors: Ding, Ning, Zhang, Xin, Zhang, Xue Di, Jing, Jun, Liu, Shan Shan, Mu, Yun Ping, Peng, Li Li, Yan, Yun Jing, Xiao, Geng Miao, Bi, Xin Yun, Chen, Hao, Li, Fang Hong, Yao, Bing, Zhao, Allan Z
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.09.2020; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Animals; Antibodies; Bacteroides; Bacteroides - isolation & purification; Chronic illnesses; Correlation of Data; Cytokines; Cytokines - analysis; Deoxyribonucleic acid; Diabetes; Diet; Diet, High-Fat - adverse effects; Digestive system; DNA; Dysbacteriosis; Dysbiosis - etiology; Dysbiosis - microbiology; Endotoxemia - microbiology; endotoxin; Epididymis; Epididymis - immunology; Epididymis - pathology; Feces - microbiology; Gastric motility; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Gene expression; Glucose; Gut Microbiota; High fat diet; Humans; Infertility; Inflammation; intestinal microbiology; Intestinal microflora; Intestine; Lymphocytes T; Macrophages; Macrophages - immunology; Male; Meiosis; Metabolic disorders; Mice; Microbiota; Microorganisms; Mitochondria; Motility; Obesity; Prevotella; Prevotella - isolation & purification; Ribonucleic acid; RNA; Sperm; Sperm Motility - immunology; Spermatogenesis; Spermatogenesis - immunology; T-Lymphocytes - immunology; Testes; Transplantation; China; intestinal microbiology; diet; inflammation; endotoxin
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2019-319127

ObjectiveHigh-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.DesignFaecal 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.ResultsTransplantation 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.ConclusionWe 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.