The Androbactome and the Gut Microbiota–Testis Axis: A Narrative Review of Emerging Insights into Male Fertility

Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota-testis axis. This narrative review introduces the conceptual term "androbactome", referring to gut microorganisms and microbial genes that are hypothesized to influence androgen biosynthesis, spermatogenesis, and broader reproductive endocrinology. The documented worldwide decline in sperm concentration heightens the urgency of clarifying microbe-mediated influences on male reproductive capacity. The synthesis of preclinical and clinical findings reveals four principal pathways by which dysbiosis compromises fertility: systemic inflammation, oxidative stress, endocrine disruption, and epigenetic alteration. Lipopolysaccharide-driven cytokinaemia, reactive oxygen species generation, hypothalamic-pituitary-gonadal axis suppression, and aberrant germ cell methylation collectively impair sperm quality and hormonal balance. Short-chain fatty acids, secondary bile acids, and indole derivatives emerge as pivotal messengers within this crosstalk. Therapeutic approaches targeting the androbactome, namely dietary optimization, probiotic or prebiotic supplementation, and fecal microbiota transplantation, have demonstrated encouraging improvements in sperm parameters and testosterone levels, yet the causal inference is constrained by predominantly cross-sectional designs and limited long-term safety data. Recognizing the androbactome as a modifiable determinant of male fertility may open new avenues for personalized diagnosis, risk stratification, and adjunctive therapy in regard to idiopathic infertility. The integration of multi-omics platforms to characterize microbial and metabolomic signatures promises to enrich diagnostic algorithms and guide precision interventions, but rigorously controlled longitudinal and interventional studies are required to secure a translational impact.