Gut microbiota and their role in male reproductive health

The gut microbiota, as the "second genome" of the human body, plays a central regulatory role in maintaining host physiological homeostasis; conversely, its dysbiosis can impair male reproductive function via the "gut-testis axis", leading to a series of pathological manifestations such as abnormal semen quality, sexual dysfunction, and reproductive organ damage. Gut microbiota exerts multidirectional effects on host metabolism, immunity, endocrinology, and the neural system, collectively forming a complex regulatory network for male reproduction. Among these, microbiota-derived metabolites such as short-chain fatty acids (SCFAs), serotonin (5-HT), and secondary bile acids, function as systemic signaling molecules that exert direct and indirect effects on the testis through blood circulation and modulation of gut barrier integrity, regulation of systemic inflammation, epigenetic reprogramming, respectively. The potential and limitations of microbiota-targeted intervention strategies, including probiotics, prebiotics, synbiotics, traditional natural herbal extracts, and fecal microbiota transplantation (FMT), are also discussed. Finally, we propose that future interventions should be tailored to individual gut microbiota profiles to achieve precise regulation of male reproductive function. This review aims to provide a new systems biology perspective for understanding the complex etiology of male infertility and to lay a theoretical foundation for the development of innovative microbiome-based diagnostic tools and therapeutic strategies.