Kaltsas Aris, Giannakodimos Ilias, Markou Eleftheria, Stavropoulos Marios, Deligiannis Dimitrios, Kratiras Zisis, Chrisofos Michael
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Department of Microbiology, University Hospital of Ioannina, 45500 Ioannina, Greece.
Int J Mol Sci. 2025 Jun 27;26(13):6211. doi: 10.3390/ijms26136211.
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.
男性不育是一个尚未得到充分认识的全球健康负担。越来越多的证据表明肠道微生物群是睾丸功能的关键调节因子，这支撑了新出现的肠道微生物群-睾丸轴。这篇叙述性综述引入了“雄激素微生物组”这一概念术语，指的是据推测会影响雄激素生物合成、精子发生及更广泛生殖内分泌学的肠道微生物和微生物基因。全球范围内有记录的精子浓度下降加剧了阐明微生物介导的对男性生殖能力影响的紧迫性。临床前和临床研究结果的综合分析揭示了生态失调损害生育能力的四条主要途径：全身炎症、氧化应激、内分泌干扰和表观遗传改变。脂多糖驱动的细胞因子血症、活性氧生成、下丘脑-垂体-性腺轴抑制以及生殖细胞异常甲基化共同损害精子质量和激素平衡。短链脂肪酸、次级胆汁酸和吲哚衍生物成为这种相互作用中的关键信使。针对雄激素微生物组的治疗方法，即饮食优化、益生菌或益生元补充以及粪便微生物群移植，已在精子参数和睾酮水平方面显示出令人鼓舞的改善，但因果推断受到主要为横断面设计和有限长期安全性数据的限制。将雄激素微生物组视为男性生育能力的一个可改变决定因素，可能为特发性不育的个性化诊断、风险分层和辅助治疗开辟新途径。整合多组学平台以表征微生物和代谢组特征有望丰富诊断算法并指导精准干预，但需要严格控制的纵向和干预性研究来确保产生转化影响。
