{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:29:53Z","timestamp":1793413793349,"version":"4.5.0"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses before 20 weeks of gestation, affects 1%\u20135% of couples of reproductive age worldwide. Growing evidence indicates a role for the microbiome in reproductive health, particularly in unexplained RPL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method of Study<\/jats:title>\n                    <jats:p>Based on a review of literature from PubMed, EMBASE, and Web of Science databases from January 2020 to September 2025, this comprehensive overview explores the current understanding of the link between microbiome dysbiosis and RPL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Microbiome dysbiosis, especially a reduction in Lactobacillus dominance and increased diversity, is strongly linked to RPL across multiple reproductive sites. RPL is associated with the loss of protective Lactobacillus crispatus and a higher presence of potentially harmful bacteria, including Gardnerella vaginalis and Atopobium vaginae. An altered gut microbiome, particularly with lipopolysaccharide\u2010producing gram\u2010negative bacteria, contributes to systemic inflammation and immune dysfunction by disrupting maternal\u2010fetal immune tolerance. The microbiome\u2010immune axis is essential for establishing maternal\u2010fetal tolerance, with dysbiosis promoting pro\u2010inflammatory Th1\/Th17 responses while suppressing regulatory T cells. Multiple mechanisms connect microbiome dysbiosis to RPL, including local inflammation, systemic immune issues, disruption of maternal\u2010fetal immune tolerance, molecular mimicry, and autoimmunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The microbiome is a promising new target for RPL treatment, with personalized microbial profiling and targeted therapies showing potential to improve pregnancy outcomes. Clinical implementation requires standardized protocols, larger randomized controlled trials, and validation of microbiome\u2010targeted interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70219","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T11:01:31Z","timestamp":1773486091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanisms and Therapeutic Implications of Microbiome\u2010Mediated Immune Dysregulation in Recurrent Pregnancy Loss and Implantation Failure"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5883-7415","authenticated-orcid":false,"given":"Wael","family":"Bahia","sequence":"first","affiliation":[{"name":"Laboratory of Clinical and Molecular Biology Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"},{"name":"Faculty of Sciences of Gafsa, Department of Biology, Campus Sidi Ahmed Zarouk University of Gafsa  Gafsa Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Soltani","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Biology Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Ferchichi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Biology Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-9757","authenticated-orcid":false,"given":"Wassim Y.","family":"Almawi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Biology Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"},{"name":"Facult\u00e9 Des Sciences de Tunis Universit\u00e9 De Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.09.023"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-024-01725-2"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gal084"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00681-4"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12124074"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00682-6"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00901-0"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01184-w"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06244"},{"key":"e_1_2_15_11_1","article-title":"The Female Reproductive Tract Microbiotas, Inflammation, and Gynecological Conditions. 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