{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:46:39Z","timestamp":1790700399038,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development","award":["JP21gk0110047"],"award-info":[{"award-number":["JP21gk0110047"]}]},{"name":"Japan Agency for Medical Research and Development","award":["JP23fk0108682"],"award-info":[{"award-number":["JP23fk0108682"]}]},{"name":"Japan Agency for Medical Research and Development","award":["JP22gn0110061"],"award-info":[{"award-number":["JP22gn0110061"]}]},{"name":"Japan Agency for Medical Research and Development","award":["20K09642"],"award-info":[{"award-number":["20K09642"]}]},{"name":"Japan Agency for Medical Research and Development","award":["23K08888"],"award-info":[{"award-number":["23K08888"]}]},{"name":"Japan Agency for Medical Research and Development","award":["24K02691"],"award-info":[{"award-number":["24K02691"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP21gk0110047"],"award-info":[{"award-number":["JP21gk0110047"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP23fk0108682"],"award-info":[{"award-number":["JP23fk0108682"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP22gn0110061"],"award-info":[{"award-number":["JP22gn0110061"]}]},{"name":"Japan Society for the Promotion of Science","award":["20K09642"],"award-info":[{"award-number":["20K09642"]}]},{"name":"Japan Society for the Promotion of Science","award":["23K08888"],"award-info":[{"award-number":["23K08888"]}]},{"name":"Japan Society for the Promotion of Science","award":["24K02691"],"award-info":[{"award-number":["24K02691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: This prospective study evaluated whether endometriosis is associated with chronic endometritis (CE) and affects the uterine endometrium microbiome (UEM) in women with repeated implantation failure (RIF). Methods: Forty-three women with RIF were divided into 12 with endometriosis (EM) and 31 without endometriosis (non-EM). The UEM was examined by 16S ribosomal RNA (rRNA) sequencing, and CE was determined by CD 138 staining (plasma cells &gt; 5.15\/10 mm2) simultaneously. Results: The EM group had a higher bacterial number (EM vs. non-EM; median [range], 6.5 vs. 3 [3\u201311, 1\u201316], p = 0.009), while the frequency of Lactobacillus species did not change. The rates of presence of Dialister (41.7% [5\/12] vs. 3.3% [1\/31], p = 0.004) and Streptococcus species (58.3% [7\/12] vs. 16.1% [5\/31], p = 0.017) were higher in the EM group. The prevalence of CE did not differ between the two groups. Multivariable logistic regression analysis revealed that the presence of Dialister species (odds ratio, 10.97, 95% confidence interval, 1.17\u2013249.37, p = 0.036) was associated with endometriosis. In the EM group, five women with Dialister species had a higher number of bacterial species (10 vs. 5 [6\u201311, 3\u20137], p = 0.021) and higher Shannon diversity index (0.50 vs. 0.20 [0.19\u20131.39, 0.03\u20130.46], p = 0.026) than seven without Dialister species. Conclusions: Dialister and Streptococcus species, and the increased number of bacterial species in UEM may be related to the pathogenesis of RIF complicated by endometriosis.<\/jats:p>","DOI":"10.3390\/jcm13164605","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T08:42:28Z","timestamp":1723020148000},"page":"4605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Uterine Endometrium Microbiome in Women with Repeated Implantation Failure Complicated by Endometriosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Yosuke","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Yamanashi, 1110 Shimokawahigashi, Chuo 409-3898, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Teine Keijinkai Hospital, 1-40, 12-chome, Maeda, Teine-ku, Sapporo 006-8555, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Mommy\u2019s Clinic Chitose, 2-1-13 Shinano, Chitose 066-0038, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Fukushi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Teine Keijinkai Hospital, 1-40, 12-chome, Maeda, Teine-ku, Sapporo 006-8555, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Yamanashi, 1110 Shimokawahigashi, Chuo 409-3898, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-4415","authenticated-orcid":false,"given":"Shinichiro","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Teine Keijinkai Hospital, 1-40, 12-chome, Maeda, Teine-ku, Sapporo 006-8555, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Yamada","sequence":"additional","affiliation":[{"name":"Center for Recurrent Pregnancy Loss, Teine Keijinkai Hospital, 1-40, 12-chome, Maeda, Teine-ku, Sapporo 006-8555, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ogc.2012.10.002","article-title":"Endometriosis and infertility: A review of the pathogenesis and treatment of endometriosis-associated infertility","volume":"39","author":"Macer","year":"2012","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1093\/humrep\/dep186","article-title":"Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome","volume":"24","author":"Stephansson","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"oceac001","DOI":"10.1093\/ehjopen\/oeac001","article-title":"Endometriosis and cardiovascular disease","volume":"2","author":"Marchandot","year":"2022","journal-title":"Eur. Heart J. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0889-8545(02)00050-5","article-title":"The epidemiology of endometriosis","volume":"30","author":"Missmer","year":"2003","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Uzuner, C., Mak, J., El-Assaad, F., and Condous, G. (2023). The bidirectional relationship between endometriosis and microbiome. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1110824"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7546047","DOI":"10.1155\/2019\/7546047","article-title":"The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases","volume":"2019","author":"Xu","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Human Microbiome Project Consortium (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486, 207\u2013214.","DOI":"10.1038\/nature11234"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Vitale, S.G., Ferrari, F., Ciebiera, M., Zgliczy\u0144ska, M., Rapisarda, A.M.C., Vecchio, G.M., Pino, A., Angelico, G., Knafel, A., and Riemma, G. (2022). The role of genital tract microbiome in fertility: A systematic review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010180"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41467-017-00901-0","article-title":"The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases","volume":"8","author":"Chen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10815-015-0614-z","article-title":"Endometrial microbiome at the time of embryo transfer: Next-generation sequencing of the 16S ribosomal subunit","volume":"33","author":"Franasiak","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ajog.2016.09.075","article-title":"Evidence that the endometrial microbiota has an effect on implantation success or failure","volume":"215","author":"Moreno","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.fertnstert.2019.05.015","article-title":"Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method","volume":"112","author":"Liu","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lozano, F.M., Lledo, B., Morales, R., Cascales, A., Hortal, M., Bernabeu, A., and Bernabeu, R. (2023). Characterization of the Endometrial Microbiome in Patients with Recurrent Implantation Failure. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030741"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gao, X., Louwers, Y., Laven, J.S.E., and Schoenmakers, S. (2024). Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010622"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Toson, B., Simon, C., and Moreno, I. (2022). The Endometrial Microbiome and Its Impact on Human Conception. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010485"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Takimoto, K., Yamada, H., Shimada, S., Fukushi, Y., and Wada, S. (2023). Chronic Endometritis and Uterine Endometrium Microbiota in Recurrent Implantation Failure and Recurrent Pregnancy Loss. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092391"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, S.R., Lee, J.C., Kim, S.H., Oh, Y.S., Chae, H.D., Seo, H., Kang, C.S., and Shin, T.S. (2021). Altered Composition of Microbiota in Women with Ovarian Endometrioma: Microbiome Analyses of Extracellular Vesicles in the Peritoneal Fluid. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094608"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/1471-0528.15916","article-title":"Endometriosis and the Microbiome: A Systematic Review","volume":"127","author":"Leonardi","year":"2020","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ma, J., Gao, W., and Li, D. (2023). Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1061766"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.jiac.2020.06.003","article-title":"Vaginal microbiota associated with preterm delivery","volume":"26","author":"Shi","year":"2020","journal-title":"J. Infect. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/rmb2.12105","article-title":"Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: A single-center pilot study","volume":"17","author":"Kyono","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.4014\/jmb.1709.09027","article-title":"Deciphering diversity indices for a better understanding of microbial communities","volume":"27","author":"Kim","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1128\/AEM.00474-06","article-title":"Introducing SONS, a tool for operational taxonomic unit-based comparisons of microbial community memberships and structures","volume":"72","author":"Schloss","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ser, H.L., Yong, S.J.A., Shafiee, M.N., Mokhtar, N.M., and Ali, R.A.R. (2023). Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review. Microorganism, 11.","DOI":"10.3390\/microorganisms11020360"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18877","DOI":"10.1038\/s41598-021-98380-3","article-title":"Endometrial microbiota is more diverse in people with endometriosis than symptomatic controls","volume":"11","author":"Wessels","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1113\/JP271694","article-title":"The vaginal microbiota, host defence and reproductive physiology","volume":"595","author":"Smith","year":"2017","journal-title":"J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Madere, F.S., Sohn, M., Winbush, A.K., Barr, B., Grier, A., Palumbo, C., Java, J., Meiring, T., Williamson, A., and Bekker, L.G. (2022). Transkingdom Analysis of the Female Reproductive Tract Reveals Bacteriophages form Communities. Viruses, 14.","DOI":"10.3390\/v14020430"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1600-0897.2011.01039.x","article-title":"Peri-conceptual cytokines\u2014Setting the trajectory for embryo implantation, pregnancy and beyond","volume":"66","author":"Robertson","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1902\/jop.1996.67.10.1103","article-title":"Periodontal infection as a possible risk factor for preterm low birth weight","volume":"67","author":"Offenbacher","year":"1996","journal-title":"J. Periodontol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1902\/jop.2007.060362","article-title":"Evidence of periopathogenic microorganisms in placentas of women with preeclampsia","volume":"78","author":"Barak","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/art.39802","article-title":"Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis","volume":"69","author":"Tito","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhong, Y., Wang, F., Meng, X., and Zhou, L. (2024). The associations between gut microbiota and inflammatory skin diseases: A bi-directional two-sample Mendelian randomization study. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1297240"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00281-020-00817-w","article-title":"The pregnancy microbiome and preterm birth","volume":"42","author":"Bayar","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1093\/humrep\/deu222","article-title":"Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis","volume":"29","author":"Khan","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejogrb.2016.01.040","article-title":"Molecular detection of intrauterine microbial colonization in women with endometriosis","volume":"199","author":"Khan","year":"2016","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e130746","DOI":"10.1172\/JCI130746","article-title":"Streptococcus pyogenes Infects Human Endometrium by Limiting the Innate Immune Response","volume":"131","author":"Weckel","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_39","first-page":"276","article-title":"Group A Streptococcal Endometritis: Report of an Outbreak and Review of the Literature","volume":"5","author":"Memish","year":"1994","journal-title":"Can. J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ono, Y., Yoshino, O., Hiraoka, T., Sato, E., Fukui, Y., Ushijima, A., Nawaz, A., Hirota, Y., Wada, S., and Tobe, K. (2020). CD206+ M2-Like Macrophages Are Essential for Successful Implantation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.557184"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1507\/endocrj.EJ18-0431","article-title":"Progesterone Governs Endometrial Proliferation-Differentiation Switching and Blastocyst Implantation","volume":"66","author":"Hirota","year":"2019","journal-title":"Endocr. J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kobayashi, H. (2023). Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20043762"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/humupd\/dmz012","article-title":"Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: A systematic review and meta-analysis","volume":"25","author":"Horton","year":"2019","journal-title":"Human Reprod. Update"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20210111","DOI":"10.1002\/EXP.20210111","article-title":"Supramolecular Nanomedicines Based on Host-Guest Interactions of Cyclodextrins","volume":"3","author":"Tong","year":"2023","journal-title":"Exploration"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"805","DOI":"10.20517\/cdr.2023.77","article-title":"Supramolecular Host-Guest Nanosystems for Overcoming Cancer Drug Resistance","volume":"6","author":"Wu","year":"2023","journal-title":"Cancer Drug Resist."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20220064","DOI":"10.1002\/VIW.20220064","article-title":"Nucleic Acid Sensors in Vivo: Challenges and Opportunities","volume":"4","author":"Liu","year":"2023","journal-title":"View"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:31:12Z","timestamp":1760110272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":46,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13164605"],"URL":"https:\/\/doi.org\/10.3390\/jcm13164605","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]}}}