{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:30:53Z","timestamp":1784302253774,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Traditional research on the female reproductive tract (FRT) microbiome has focused on the dominance of bacteria, particularly\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      , as a marker of health. This bacteriocentric paradigm, however, cannot fully explain clinical enigmas like the high recurrence of bacterial vaginosis (BV) or the persistence of HPV infection. This review introduces a new pan-microbiome framework that highlights the overlooked roles of the virome and mycobiome as the ecosystem\u2019s neglected components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic scoping review following the PRISMA-ScR guidelines. We searched PubMed, Embase, and Web of Science databases for studies published up to October 2025. Inclusion criteria focused on original research and metagenomic studies examining the female reproductive tract (FRT) virome, mycobiome, and bacteriome, specifically their interactions and clinical associations with bacterial vaginosis (BV) and HPV persistence. Data were extracted and synthesized to evaluate the pan-microbiome framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The virome and mycobiome, despite their low biomass, are increasingly recognized as potential ecosystem modulators. Bacteriophages, for instance, are proposed to act as community \u201cmodulators,\u201d either through lytic cycles that maintain bacterial diversity or lysogenic cycles that may contribute to stabilizing pathogenic biofilms in dysbiosis like BV by introducing virulence genes. Similarly, fungi like\n                      <jats:italic>Candida<\/jats:italic>\n                      can transition from harmless commensals to pathogens when the protective bacterial balance is disturbed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FRT health is an emergent property of the complex interactions among bacteria, viruses, and fungi. A comprehensive understanding requires a pan-microbiome perspective. Future therapeutic strategies should move beyond a \u201cone-bug, one-drug\u201d approach toward \u201cecosystem restoration,\u201d using targeted methods like phage therapy or vaginal microbiota transplantation to attempt to restore the balance of the entire microbial community.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1749584","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:00:33Z","timestamp":1775800833000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["What is the impact of the virome and mycobiome on female reproductive tract health? A systematic scoping review"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingya","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualei","family":"Dai","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, The Affiliated Hospital of Yunnan University, Yunnan University","place":["Kunming, Yunnan, China"]},{"name":"School of Medicine, Yunnan University","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00181-21","article-title":"Roles of the microbiota of the female reproductive tract in gynecological and reproductive health","volume":"86","author":"Zhu","year":"2022","journal-title":"Microbiol Mol Biol Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00181","article-title":"The vaginal microenvironment: The physiologic role of lactobacilli","volume":"5","author":"Amabebe","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.631972","article-title":"The female vaginal microbiome in health and bacterial vaginosis","volume":"11","author":"Chen","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.medmic.2023.100082","article-title":"Bacterial vaginosis: A state of microbial dysbiosis","volume":"16","author":"Mondal","year":"2023","journal-title":"Med Microecol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16020399","article-title":"Human papillomavirus infections and the role played by cervical and cervico-vaginal microbiota\u2014evidence from next-generation sequencing studies","volume":"16","author":"G\u0142owienka-Stodolak","year":"2024","journal-title":"Cancers"},{"key":"B6","doi-asserted-by":"publisher","first-page":"7806","DOI":"10.1038\/s41467-025-63162-2","article-title":"Metagenomic analysis reveals how multiple stressors disrupt virus-host interactions in multi-trophic freshwater mesocosms","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41522-025-00747-1","article-title":"Metagenomic insight into the vaginal microbiome in women infected with HPV 16 and 18","volume":"11","author":"Jung","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01751-5","article-title":"A multi-kingdom collection of 33,804 reference genomes for the human vaginal microbiome","volume":"9","author":"Huang","year":"2024","journal-title":"Nat Microbiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41522-025-00682-1","article-title":"Strain-level variation among vaginal Lactobacillus crispatus and Lactobacillus iners as identified by comparative metagenomics","volume":"11","author":"Nori","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01447-2","article-title":"Bacterial amylases enable glycogen degradation by the vaginal microbiome","volume":"8","author":"Jenkins","year":"2023","journal-title":"Nat Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-023-02916-8","article-title":"Glycogen availability and pH variation in a medium simulating vaginal fluid influence the growth of vaginal Lactobacillus species and Gardnerella vaginalis","volume":"23","author":"Navarro","year":"2023","journal-title":"BMC Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0321737","article-title":"In vivo assessment of the effect of gel containing lactic acid and glycogen on vaginal microbiota and pH of asymptomatic women of reproductive age","volume":"20","author":"Campaner","year":"2025","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"20798","DOI":"10.1038\/s41598-025-08321-7","article-title":"Comparative genomic analysis of bacteriocin genes in Lactobacillus crispatus strains","volume":"15","author":"Santarelli","year":"2025","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41522-025-00788-6","article-title":"Impact of a multi-strain L. crispatus-based vaginal synbiotic on the vaginal microbiome: a randomized placebo-controlled trial","volume":"11","author":"Ravel","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00983-25","article-title":"Lactobacillus iners dominates the vaginal microbiota of healthy Italian women of reproductive age","volume":"10","author":"Vinerbi","year":"2025","journal-title":"mSystems"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/6079734","article-title":"Lactobacillus iners is associated with vaginal dysbiosis in healthy pregnant women: a preliminary study","volume":"2019","author":"Zheng","year":"2019","journal-title":"BioMed Res Int"},{"key":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41392-025-02152-8","article-title":"Population-level analyses identify host and environmental variables influencing the vaginal microbiome","volume":"10","author":"Qin","year":"2025","journal-title":"Signal Transduction Targeted Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1186\/s12866-025-04236-5","article-title":"Shallow shotgun metagenomic sequencing of vaginal microbiomes with the Oxford Nanopore technology enables the reliable determination of vaginal community state types and broad community structures","volume":"25","author":"Graeber","year":"2025","journal-title":"BMC Microbiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.113473","article-title":"Lactobacillus-rich cervicovaginal microbiome associated with lower BV, HPV, and cytology outcomes in women","volume":"28","author":"Osei Sekyere","year":"2025","journal-title":"iScience"},{"key":"B21","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/pathogens10020247","article-title":"Atopobium vaginae and Prevotella bivia are able to incorporate and influence gene expression in a pre-formed Gardnerella vaginalis biofilm","volume":"10","author":"Castro","year":"2021","journal-title":"Pathogens"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.824860","article-title":"Six bacterial vaginosis-associated species can form an in vitro and ex vivo polymicrobial biofilm that is susceptible to Thymbra capitata essential oil","volume":"12","author":"Rosca","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.3390\/v12101143","article-title":"Characterization of the vaginal DNA virome in health and dysbiosis","volume":"12","author":"Jakobsen","year":"2020","journal-title":"Viruses"},{"key":"B24","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3390\/v14020430","article-title":"Transkingdom analysis of the female reproductive tract reveals bacteriophages form communities","volume":"14","author":"Madere","year":"2022","journal-title":"Viruses"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010400","article-title":"From kill the winner to eliminate the winner in open phage-bacteria systems","volume":"18","author":"Marantos","year":"2022","journal-title":"PloS Comput Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.3390\/v13122341","article-title":"Presence and persistence of putative lytic and temperate bacteriophages in vaginal metagenomes from South African adolescents","volume":"13","author":"Happel","year":"2021","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/evo.14153","article-title":"Fitness benefits to bacteria of carrying prophages and prophage-encoded antibiotic-resistance genes peak in different environments","volume":"75","author":"Wendling","year":"2021","journal-title":"Evolution"},{"key":"B28","doi-asserted-by":"publisher","first-page":"000726","DOI":"10.1099\/mgen.0.000726","article-title":"Prophages encoding human immune evasion cluster genes are enriched in Staphylococcus aureus isolated from chronic rhinosinusitis patients with nasal polyps","volume":"7","author":"Nepal","year":"2021","journal-title":"Microb Genom"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054379","article-title":"Characterization of the vaginal micro- and mycobiome in asymptomatic reproductive-age Estonian women","volume":"8","author":"Drell","year":"2013","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009884","article-title":"A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis","volume":"17","author":"Liu","year":"2021","journal-title":"PloS Pathog"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01117","article-title":"Biofilm formation of Candida albicans facilitates fungal infiltration and persister cell formation in vaginal candidiasis","volume":"11","author":"Wu","year":"2020","journal-title":"Front Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/iai.72.5.2939-2946.2004","article-title":"An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis","volume":"72","author":"Fidel","year":"2004","journal-title":"Infect Immun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.10.008","article-title":"Associations between the vaginal microbiome and Candida colonization in women of reproductive age","volume":"222","author":"Tortelli","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1153894","article-title":"Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations","volume":"13","author":"Liu","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/s0020-7292(00)00350-7","article-title":"Vaginal candidosis: epidemiological and etiological factors","volume":"71","author":"Ferrer","year":"2000","journal-title":"Int J Gynaecol Obstet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03501-23","article-title":"Vaginal fungi are associated with treatment-induced shifts in the vaginal microbiota and with a distinct genital immune profile","volume":"12","author":"Armstrong","year":"2024","journal-title":"Microbiol Spectr"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/froh.2021.689382","article-title":"Anticandidal activities by Lactobacillus species: An update on mechanisms of action","volume":"2","author":"Vazquez-Munoz","year":"2021","journal-title":"Front Oral Health"},{"key":"B38","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3390\/microorganisms12010108","article-title":"Bacterial vaginosis and vulvovaginal candidiasis pathophysiologic interrelationship","volume":"12","author":"Sobel","year":"2024","journal-title":"Microorganisms"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.453654","article-title":"Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis","volume":"288","author":"Lewis","year":"2013","journal-title":"J Biol Chem"},{"key":"B40","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/j.1600-0897.2011.01089.x","article-title":"Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands","volume":"67","author":"Mirmonsef","year":"2012","journal-title":"Am J Reprod Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3892\/br.2023.1626","article-title":"Gut and reproductive tract microbiota: Insights into the pathogenesis of endometriosis (review)","volume":"19","author":"Kobayashi","year":"2023","journal-title":"BioMed Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.3390\/biomedicines13061332","article-title":"Impact of the female genital microbiota on outcomes of assisted reproductive techniques","volume":"13","author":"Fasoulakis","year":"2025","journal-title":"Biomedicines"},{"key":"B43","article-title":"Vaginal microbiome dysbiosis in preterm birth. Progress in molecular biology and translational science","author":"Ahrodia","year":"2022"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1086\/503780","article-title":"High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence","volume":"193","author":"Bradshaw","year":"2006","journal-title":"J Infect Dis"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s2666-5247(22)00043-x","article-title":"Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial","volume":"3","author":"Armstrong","year":"2022","journal-title":"Lancet Microbe"},{"key":"B46","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/pathogens10010054","article-title":"Engineered phage endolysin eliminates Gardnerella biofilm without damaging beneficial bacteria in bacterial vaginosis ex vivo","volume":"10","author":"Landlinger","year":"2021","journal-title":"Pathogens"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46110778","article-title":"Optimized protocol for RNA isolation from Penicillium spp. and Aspergillus fumigatus strains","volume":"46","author":"Siniecka-Kotula","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.3390\/ijms23042181","article-title":"Metagenomic sequencing for microbial DNA in human samples: Emerging technological advances","volume":"23","author":"Shi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2022.02.007","article-title":"Microbial dark matter: From discovery to applications","volume":"20","author":"Zha","year":"2022","journal-title":"Genomics Proteomics Bioinf"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.05.015","article-title":"Finding the missing links among metabolites, microbes, and the host","volume":"40","author":"Dorrestein","year":"2014","journal-title":"Immunity"},{"key":"B51","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.mib.2019.09.011","article-title":"Timescales of gut microbiome dynamics","volume":"50","author":"Schlomann","year":"2019","journal-title":"Curr Opin Microbiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011649","article-title":"Virus-host interactions predictor (VHIP): Machine learning approach to resolve microbial virus-host interaction networks","volume":"20","author":"Bastien","year":"2024","journal-title":"PloS Comput Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/oodh\/oqaf027","article-title":"Gender and racial bias unveiled: clinical artificial intelligence (AI) and machine learning (ML) algorithms are fanning the flames of inequity","volume":"3","author":"Otokiti","year":"2025","journal-title":"Oxf Open Digit Health"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2021.100347","article-title":"Addressing bias in big data and AI for health care: A call for open science","volume":"2","author":"Norori","year":"2021","journal-title":"Patterns (N Y)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/s41598-025-85420-5","article-title":"External validation of an artificial intelligence model using clinical variables, including ICD-10 codes, for predicting in-hospital mortality among trauma patients: a multicenter retrospective cohort study","volume":"15","author":"Lee","year":"2025","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1749584\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:00:34Z","timestamp":1775800834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1749584\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":55,"alternative-id":["10.3389\/fimmu.2026.1749584"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1749584","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"article-number":"1749584"}}