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Evidence for a local microbiome largely derives from bacterial nucleic acid detection; however, the biological relevance of these signals remains debated, with whether they reflect viable microbial communities, transient colonisation, or mere microbial remnants with immunomodulatory effects. Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators of host\u2013microbiota crosstalk. Their small size enables them to traverse tissue barriers, enter systemic circulation and access barrier\u2010protected anatomical sites like the placenta, thereby extending their biological reach beyond the site of origin. Although BEVs have been extensively characterised in the context of gastrointestinal, respiratory and systemic diseases, their relevance within the reproductive tract remains insufficiently defined. Understanding whether BEVs contribute to processes such as endometrial receptivity, gamete interaction, embryo implantation and immune tolerance in early pregnancy may reveal novel mechanisms of reproductive physiology and pathology. Furthermore, unravelling the role of BEVs could help resolve the ongoing debate regarding the existence of a functional upper reproductive tract (URT) microbiota, reframing it in terms of microbial activity rather than microbial presence alone. This review synthesises the limited but growing body of evidence on BEVs in the reproductive tract, with a particular emphasis on their potential influence on female fertility and early pregnancy outcomes. We also outline the major methodological challenges, including the discrimination of BEVs from host\u2010derived extracellular vesicles (EVs), the technical limitations of current detection approaches and the risk of contamination in low\u2010biomass environments that complicate research in this field. Finally, we highlight conceptual frameworks and future research directions needed to establish BEVs as important players in reproductive biology and to harness their diagnostic and therapeutic potential in reproductive medicine.<\/jats:p>","DOI":"10.1002\/jev2.70296","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:35:21Z","timestamp":1778866521000},"source":"Crossref","is-referenced-by-count":1,"title":["Bacterial Extracellular Vesicles: New Hype or Hope to Explain Reproductive Host\u2013Microbiota Interactions"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4360-3808","authenticated-orcid":false,"given":"Hannah","family":"Wein","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology University Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6676-8537","authenticated-orcid":false,"given":"Paula","family":"Iglesias\u2010Moreno","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institute  Huddinge Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2507-5735","authenticated-orcid":false,"given":"Apostol","family":"Apostolov","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institute  Huddinge Stockholm Sweden"},{"name":"Department of Gynecology and Reproductive Medicine Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Celvia CC AS Tartu Estonia"},{"name":"Department of Biotechnology Institute of Molecular and Cell Biology University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-8160","authenticated-orcid":false,"given":"Andres","family":"Salumets","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institute  Huddinge Stockholm Sweden"},{"name":"Department of Gynecology and Reproductive Medicine Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Celvia CC AS Tartu Estonia"},{"name":"Department of Obstetrics and Gynecology Institute of Clinical Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-8551","authenticated-orcid":false,"given":"Dami\u00e1n O.","family":"Muzzio","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-1532","authenticated-orcid":false,"given":"Alberto","family":"Sola\u2010Leyva","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institute  Huddinge Stockholm Sweden"},{"name":"Department of Gynecology and Reproductive Medicine Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Celvia CC AS Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008599"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.165"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2012.174"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8121996"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.019"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010022\u201001317\u20109"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02181"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoaf010"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.15130"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.70073"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601199"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy012"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/whe.15.44"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.16.4725\u20104733.1999"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","unstructured":"Bl\u00fcmer N. 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