Jin Jing, Yim Howard Chi Ho, Chang Hsiao Mei Ellie, Wang Yiwei, Choy Kathleen Hoi Kei, Chan Sze Yan, Alqawasmeh Odai A M, Liao Jinyue, Jiang Xiao-Tao, Chan David Yiu Leung, Fok Ellis Kin Lam
Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR.
Faculty of Medicine and Health, Microbiome Research Centre, St George and Sutherland Campus, School of Clinical Medicine, The University of New South Wales, Sydney 2217, Australia.
PNAS Nexus. 2024 Sep 19;3(10):pgae419. doi: 10.1093/pnasnexus/pgae419. eCollection 2024 Oct.
Infertility is associated with the alteration of the seminal microbiome. However, the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility. While we observed comparable genera, diversity and evenness of bacterial communities, a marked decrease in the modularity of the metacommunities was observed in patients with abnormal spermiogram ( = 57) as compared to the control ( = 30). A marked elevation of DEFB119 was observed in a subpopulation of male infertile patients ( = 5). Elevated seminal DEFB119 was associated with a decrease in the observed genera, diversity and evenness of bacterial communities, and further distortion of the metacommunities. Mediation analysis suggests the involvement of elevated DEFB119 and dysbiosis of the seminal microbiome in mediating the abnormalities in the spermiogram. Functional experiments showed that recombinant DEFB119 significantly decrease the progressive motility of sperm in patients with abnormal spermiogram. Moreover, DEFB119 demonstrated species-specific antimicrobial activity against common seminal and nonseminal species. Our work identifies an important host factor that mediates the host-microbiome interaction and stratifies the seminal microbiome associated with male infertility. These results may lead to a new diagnostic method for male infertility and regimens for formulating the microbiome in the reproductive tract and other organ systems.
不育与精液微生物群的改变有关。然而，生态失调的发病机制仍存在争议，宿主因素的作用也尚不明确。本研究调查了男性不育患者精液微生物群的变化，并探讨了生殖道特异性宿主抗菌肽DEFB119与精液微生物群及男性生育能力之间的关联和功能。虽然我们观察到细菌群落的属、多样性和均匀度具有可比性，但与对照组（n = 30）相比，精子ogram异常患者（n = 57）的元群落模块性显著降低。在一部分男性不育患者（n = 5）中观察到DEFB119显著升高。精液中DEFB119升高与观察到的细菌群落属、多样性和均匀度降低以及元群落的进一步扭曲有关。中介分析表明，DEFB119升高和精液微生物群生态失调参与介导精子ogram异常。功能实验表明，重组DEFB119显著降低了精子ogram异常患者精子的前向运动能力。此外，DEFB119对常见的精液和非精液物种表现出种特异性抗菌活性。我们的研究确定了一个重要的宿主因素，它介导宿主-微生物群相互作用，并对与男性不育相关的精液微生物群进行分层。这些结果可能会导致一种新的男性不育诊断方法，以及制定生殖道和其他器官系统微生物群的方案。
