Mowla Shahriar, Farahani Linda, Tharakan Tharu, Davies Rhianna, Correia Goncalo D S, Lee Yun S, Kundu Samit, Khanjani Shirin, Sindi Emad, Rai Raj, Regan Lesley, Khalifa Dalia, Henkel Ralf, Minhas Suks, Dhillo Waljit S, Ben Nagi Jara, Bennett Phillip, MacIntyre David A, Jayasena Channa N
Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
Wolfson Fertility Unit, Department of Gynaecology, St. Mary's Hospital, Imperial College NHS Trust, London, United Kingdom.
Elife. 2025 May 8;13:RP96090. doi: 10.7554/eLife.96090.
Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could elucidate its potential role in clinical management. We used semen analysis, terminal-deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate-nick-end-labelling, Comet DNA fragmentation, luminol reactive oxidative species (ROS) chemiluminescence, and metataxonomic profiling of semen microbiota by 16S rRNA amplicon sequencing in this prospective, cross-sectional study to investigate composition and bacterial load of seminal bacterial genera and species, semen parameters, ROS, and sperm DNA fragmentation in men with reproductive disorders and proven fathers. 223 men were enrolled, including healthy men with proven paternity (n=63), the male partners in a couple encountering RPL (n=46), men with male factor infertility (n=58), and the male partners of couples with unexplained infertility (n=56). Rates of high sperm DNA fragmentation, elevated ROS, and oligospermia were more prevalent in the study group compared with control. In all groups, semen microbiota clustered into three major -dominant groups (1, ; 2, ; 3, and ); no species clusters were identified. Group 2 had the highest microbial richness (p<0.001), alpha-diversity (p<0.001), and bacterial load (p<0.0001). Overall bacterial composition or load has not been found to associate with semen analysis, ROS, or DNA fragmentation. Whilst global perturbation of the seminal microbiota is not associated with male reproductive disorders, men with unidentified seminal are more likely to have abnormal seminal analysis. Future studies may elucidate if reduction has therapeutic potential.
多项研究已将精液微生物群异常与男性不育联系起来，但由于样本量有限或分析深度不足，结果各异。复发性流产（RPL）期间的精液微生物群尚未得到研究。全面评估患有生殖障碍男性的精液微生物群，可能会阐明其在临床管理中的潜在作用。在这项前瞻性横断面研究中，我们使用精液分析、末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记、彗星DNA片段化、鲁米诺活性氧化物种（ROS）化学发光以及通过16S rRNA扩增子测序对精液微生物群进行宏分类分析，以研究患有生殖障碍男性和已证实有生育能力男性的精液细菌属和种的组成、细菌载量、精液参数、ROS和精子DNA片段化情况。共纳入223名男性，包括有生育能力的健康男性（n = 63）、经历复发性流产夫妇中的男性伴侣（n = 46）、患有男性因素不育的男性（n = 58）以及患有不明原因不育夫妇中的男性伴侣（n = 56）。与对照组相比，研究组中精子DNA高片段化、ROS升高和少精子症的发生率更高。在所有组中，精液微生物群聚为三个主要优势组（1， ；2， ；3， 和 ）；未识别出物种簇。第2组具有最高的微生物丰富度（p < 未识别出物种簇。第2组具有最高的微生物丰富度（p < 0.001）、α多样性（p < 0.001）和细菌载量（p < 0.0001）。未发现总体细菌组成或载量与精液分析、ROS或DNA片段化有关。虽然精液微生物群的整体扰动与男性生殖障碍无关，但精液不明原因异常的男性更有可能精液分析异常。未来的研究可能会阐明减少这种异常是否具有治疗潜力。 0.001）、α多样性（p < 0.001）和细菌载量（p < 0.0001）。未发现总体细菌组成或载量与精液分析、ROS或DNA片段化有关。虽然精液微生物群的整体扰动与男性生殖障碍无关，但精液不明原因异常的男性更有可能精液分析异常。未来的研究可能会阐明减少这种异常是否具有治疗潜力。
