Gut Microbiota Mitigates High Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome

Background: High fat diet (HFD)-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. The aim of this investigation was designed to explore the role of alginate oligosaccharide (AOS)-benefited gut microbiota in rescuing HFD-impaired spermatogenesis and male fertility. Methods: Faecal microbes derived from AOS dosed mice (A10-FMT) were transplanted to the mice fed with HFD. The sperm concentration and motility, pregnant rate, the number of pup/litter, gut microbes, protein expression for spermatogenesis process and lipid metabolism related proteins, blood and testicular metabolites were determined. Findings: We discovered that A10-FMT improved HFD-decreased semen quality and male fertility by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroidales and decreasing Mucispirillum. And A10-FMT benefited gut microbiota to improve liver function through adjusting lipid metabolism to produce n-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), thus to ameliorate HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. Interpretations: Our studies highlight the possibility of treating male infertility using AOS-benefited gut microbiota, especially for those with obesity and metabolic issues. Funding Information: This study was supported by the National Natural Science Foundation of China (31772408 to YZ; 31672428 to HZ). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All animal procedures used in this study were approved by the Animal Care and Use Committee of the Institute of Animal Sciences of Chinese Academy of Agricultural Sciences (IAS2020-106).