Micromanagement: how the male reproductive microbiome shapes male fertility

IMPORTANCE: One in six couples worldwide experience infertility, and male factors contribute to at least half of these cases. The pathophysiology of male infertility is complex and often multifactorial, and the male reproductive microbiome has now been implicated as a potentially critical component in male reproductive health and disease. OBJECTIVE: To summarize the emerging evidence describing the male reproductive microbiome with a focus on clinically relevant aspects within spermatogenesis and reproductive outcomes. EVIDENCE REVIEW: We performed a librarian-led search of MEDLINE, Embase, and Web of Science and a targeted PubMed search for antibiotic and probiotic trials, focusing on human studies that reported male reproductive microbiome data together with semen parameters, oxidative, deoxyribonucleic acid (DNA)-damage, or inflammatory indices, or assisted reproduction outcomes. Given heterogeneity in design and laboratory methods, we conducted a narrative synthesis and integrated relevant mechanistic animal work. FINDINGS: Across heterogeneous cohorts, anaerobe-leaning seminal profiles (often with Prevotella or Atopobium) are more often linked to higher oxidative stress, greater sperm DNA fragmentation, and lower motility or total motile count. In contrast, Lactobacillus-rich profiles more often align with better redox status and DNA integrity. Couple-level data show rapid and robust partner microbiome exchange that can shift semen over short periods. Work on the gut-testis axis has identified a link between gut dysbiosis and systemic inflammation with semen quality via the gut-testis axis. Proposed mechanisms underlying the effect of the microbiome on fertility include local inflammation, oxidative injury, altered seminal rheology (e.g., viscosity/viscoelastic properties of seminal plasma), adherence/biofilms, and immune-metabolic crosstalk. Small trials to date using antibiotics and/or probiotics show variable benefits; durability and reproductive endpoints remain limited. CONCLUSION AND RELEVANCE: Emerging evidence supports a role for the male reproductive microbiome in sperm function and fertility and highlights it as a potential target for clinical intervention. However, predominantly small, cross-sectional studies and methodological heterogeneity limit causal inference and immediate translation, underscoring the need for longitudinal, couple-integrated cohorts and adequately powered randomized trials of targeted microbiome modulation.