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(2) Methods: Here, we performed comprehensive clinical analyses and gut microbial profiling using shotgun metagenomic sequencing in patients with NOA and control individuals. (3) Results: The gut microbial alpha and beta diversity significantly differed between patients with NOA and controls. Several microbial strains, including Bacteroides vulgatus and Streptococcus thermophilus, were significantly more abundant in the NOA group, whereas Bacteroides thetaiotaomicron and Parabacteroides sp. CT06 were enriched in the control group. Moreover, functional pathway analysis suggested that the altered microbiota in NOA suppressed the carbohydrate metabolism pathway, while amino acid metabolism and methane metabolism pathways were enhanced. We observed that the differential microbial species, such as Acinetobacter johnsonii, had a strong correlation with clinical parameters, including age, body mass index, testosterone, and follicle-stimulating hormone. Communication and interplay among microbial genera were significantly increased in NOA than in the control group. (4) Conclusions: Altered microbial composition and functional pathways in the NOA group were revealed, which highlight the utility of gut microbiota in understanding microbiota-related pathogenesis of NOA and might be helpful to the clinical management of NOA.<\/jats:p>","DOI":"10.3390\/jcm12020701","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T04:31:32Z","timestamp":1673843492000},"page":"701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Characterization of Non-Obstructive Azoospermia in Men Using Gut Microbial Profiling"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-5547","authenticated-orcid":false,"given":"Yalei","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Urology, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-4660","authenticated-orcid":false,"given":"Zirun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0334-6467","authenticated-orcid":false,"given":"Jing","family":"Hang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China"},{"name":"Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing 100191, China"},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University First Hospital, Institute of Urology, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3498-3095","authenticated-orcid":false,"given":"Huajun","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Cancer Hospital and Institute, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-2362","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University Third Hospital, Beijing 100191, China"},{"name":"Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility: Definition and epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. 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