The influence and mechanism of gut microbiota on spermatogenesis

Gut microbiota (GM) serves several functions in host, including immunological modulation, maintaining intestinal epithelial cell barrier and defending against pathogen invasion. Previous research has demonstrated that GM could regulate distal organs such as gut-brain and gut-liver axis. Recently, a rising number of researchers have discovered the substantial link between GM alteration and spermatogenesis disorder in male. This review highlights the phenomena of sperm production abnormalities caused by GM dysbiosis and the putative molecular pathways. Microbiota dysbiosis could lead to abnormal sperm production through multiple pathways. For example, the metabolic disturbance of vitamins impairs meiosis and spermatogenesis, upregulated miR-211-5p of extracellular vesicles inhibits meiosis and damages spermatogenesis, abnormal sphingolipid metabolite affects spermatogenic cell apoptosis, decreased short-chain fatty acid level causes inflammation and damages testicular tissue and reduced androgen level, resulting in spermatogenesis disorder. In addition, this review highlights therapeutic strategies, such as the administration of vitamins, probiotics, and prebiotics, for the treatment of spermatogenesis disorders associated with GM dysregulation. These insights underscore the importance of targeting the GM to preserve sperm quality and improve male reproductive health, offering promising future directions for the treatment of spermatogenic dysfunction and infertility.