{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:20Z","timestamp":1788419780774,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n Vulvovaginal candidiasis (VVC) is a common mucosal infection predominantly attributed to\n Candida albicans<\/jats:italic>\n (\n C. albicans<\/jats:italic>\n ). However, this yeast frequently colonizes the vaginal niche without causing symptoms, indicating that additional microbial and host factors might contribute to disease onset and\/or pathology. This study investigated whether VVC is associated with a shift in the vaginal microbiota.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Vaginal samples from 96 non-pregnant women were stratified into three study groups: healthy (NEG,\n n<\/jats:italic>\n \u202f=\u202f54), asymptomatic (ASYMP,\n n<\/jats:italic>\n \u202f=\u202f20), and symptomatic (SYMP,\n n<\/jats:italic>\n \u202f=\u202f22). Vaginal pH, PMN infiltration, and\n C. albicans<\/jats:italic>\n morphology in vaginal samples were assessed microscopically, while fungal load was quantified by qPCR and isolates were tested for hyphal formation and biofilm production. Vaginal microbiota was analyzed by 16S rRNA amplicon sequencing on a subset of 43 representative vaginal samples.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Most SYMP women exhibited a characteristic inflammatory profile, with 75% showing a vaginal pH\u202f\u2265\u202f4.5, 95.45% presenting marked PMN infiltration (score 2) and all displaying filamentous\n C. albicans<\/jats:italic>\n forms\n in vivo<\/jats:italic>\n . In contrast, 90.91% of ASYMP women had a vaginal pH 4.5, none showed PMN infiltration (score 0), and 65% displayed the fungus exclusively in the yeast form. The vaginal burden of\n C. albicans<\/jats:italic>\n DNA was 4.9-fold higher in SYMP than in ASYMP women. Of interest, symptomatic disease was associated with the selective co-enrichment of the anaerobic bacteria\n Dialister micraerophilus<\/jats:italic>\n and\n Aerococcus christensenii<\/jats:italic>\n , which emerged as the main microbial features distinguishing SYMP from ASYMP women. Notably, the relative abundance of\n Dialister micraerophilus<\/jats:italic>\n positively correlated with both PMN infiltration score and vaginal pH.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings identify\n Dialister micraerophilus<\/jats:italic>\n and\n Aerococcus christensenii<\/jats:italic>\n as key anaerobic bacterial signatures associated with VVC. Further studies are needed to assess the possible role of these bacteria in VVC causation or modification.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1939688","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:42:56Z","timestamp":1788417776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Candida albicans and anaerobic bacterial co-expansion in vulvovaginal candidiasis: a cross-sectional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Luigi","family":"Tordelli Ruda","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loris","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"BMR Genomics s.r.l.","place":["Padova, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pedretti","sequence":"additional","affiliation":[{"name":"HIP-TECH PhD Program, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samyr","family":"Kenno","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Sabbatini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Roselletti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bozza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Gaziano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Pericolini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ardizzoni","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Monari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1128\/CMR.00076-09","article-title":"Candida infections of the genitourinary tract","volume":"23","author":"Achkar","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"100877","DOI":"10.1016\/j.currproblcancer.2022.100877","article-title":"The vaginal microbiome: a complex milieu affecting risk of human papillomavirus persistence and cervical cancer","volume":"46","author":"Alimena","year":"2022","journal-title":"Curr. Probl. Cancer"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.3390\/microorganisms9051069","article-title":"Study of the vaginal microbiota in healthy women of reproductive age","volume":"9","author":"Alonzo Mart\u00ednez","year":"2021","journal-title":"Microorganisms"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"692491","DOI":"10.3389\/fmicb.2021.692491","article-title":"It takes two to tango: how a dysregulation of the innate immunity, coupled with Candida virulence, triggers VVC onset","volume":"12","author":"Ardizzoni","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/jof3040057","article-title":"Global and multi-national prevalence of fungal diseases\u2014estimate precision","volume":"3","author":"Bongomin","year":"2017","journal-title":"J. Fungi"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1186\/s12866-015-0608-0","article-title":"Lactobacillus crispatus inhibits growth of Gardnerella vaginalis and Neisseria gonorrhoeae on a porcine vaginal mucosa model","volume":"15","author":"Breshears","year":"2015","journal-title":"BMC Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2174\/1874285801610010027","article-title":"Aerococcus christensenii as part of severe polymicrobial chorioamnionitis in a pregnant woman","volume":"10","author":"Carlstein","year":"2016","journal-title":"Open Microbiol. J."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"14095","DOI":"10.1038\/s41598-019-50410-x","article-title":"Diversity of vaginal microbiome and metabolome during genital infections","volume":"9","author":"Ceccarani","year":"2019","journal-title":"Sci. Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1099\/00207713-49-3-1125","article-title":"Note: Aerococcus christensenii sp. nov., from the human vagina","volume":"49","author":"Collins","year":"1999","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e339","DOI":"10.1016\/S1473-3099(18)30103-8","article-title":"Global burden of recurrent vulvovaginal candidiasis: a systematic review","volume":"18","author":"Denning","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1093\/infdis\/jiaa459","article-title":"Association between vaginal bacterial microbiota and vaginal yeast colonization","volume":"223","author":"Eastment","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.3390\/microorganisms11051211","article-title":"The interplay between Candida albicans, vaginal mucosa, host immunity and resident microbiota in health and disease: an overview and future perspectives","volume":"11","author":"Gaziano","year":"2023","journal-title":"Microorganisms"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"643422","DOI":"10.3389\/fmicb.2021.643422","article-title":"Role of vaginal microbiota dysbiosis in gynecological diseases and the potential interventions","volume":"12","author":"Han","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/jof11070501","article-title":"Vaginal clinical isolates of Candida albicans differentially modulate complosome activation in vaginal epithelial cells","volume":"11","author":"Kenno","year":"2025","journal-title":"J. Fungi"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0152124","DOI":"10.1128\/spectrum.01521-24","article-title":"Highlight signatures of vaginal microbiota and metabolome contributed to the occurrence and recurrence of vulvovaginal candidiasis","volume":"12","author":"Liang","year":"2024","journal-title":"Microbiol. Spectrum"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s10142-025-01730-x","article-title":"Aerococcus christensenii: an emerging pathogen associated with infections and bacteremia in pregnancy\u2014genomic insights and pathogenicity evaluation","volume":"25","author":"Lin","year":"2025","journal-title":"Funct. Integr. Genomics"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/1471-2164-11-488","article-title":"Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis","volume":"11","author":"Ling","year":"2010","journal-title":"BMC Genomics"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1146\/annurev-micro-092611-150157","article-title":"Vaginal microbiome: rethinking health and disease","volume":"66","author":"Ma","year":"2012","journal-title":"Ann. Rev. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"27799","DOI":"10.3402\/mehd.v26.27799","article-title":"Changes in vaginal microbiota following antimicrobial and probiotic therapy","volume":"26","author":"Macklaim","year":"2015","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"10.1128\/msystems.00622-21","DOI":"10.1128\/msystems.00622-21","article-title":"Recurrent vulvovaginal candidiasis: a dynamic interkingdom biofilm disease of Candida and Lactobacillus","volume":"6","author":"McKloud","year":"2021","journal-title":"mSystems"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e0272012","DOI":"10.1371\/journal.pone.0272012","article-title":"Association of key species of vaginal bacteria of recurrent bacterial vaginosis patients before and after oral metronidazole therapy with short- and long-term clinical outcomes","volume":"17","author":"Mollin","year":"2022","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/1471-0528.14209","article-title":"Bacterial vaginosis: a critical analysis of current knowledge","volume":"124","author":"Nasioudis","year":"2017","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"273","DOI":"10.4103\/0366-6999.198927","article-title":"Lactobacillus crispatus modulates vaginal epithelial cell innate response to Candida albicans","volume":"130","author":"Niu","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"458","DOI":"10.2337\/cd23-0011","article-title":"Diabetes and vulvovaginal conditions","volume":"41","author":"O\u2019Laughlin","year":"2023","journal-title":"Clin. Diabetes"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.3390\/microorganisms10102091","article-title":"Vaginal Lactobacillus impair Candida dimorphic switching and biofilm formation","volume":"10","author":"Parolin","year":"2022","journal-title":"Microorganisms"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0131220","DOI":"10.1371\/journal.pone.0131220","article-title":"Isolation of vaginal lactobacilli and characterization of anti-Candida activity","volume":"10","author":"Parolin","year":"2015","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","DOI":"10.21203\/rs.3.rs-2778207\/v1","article-title":"Multi-group analysis of compositions of microbiomes with covariate adjustments and repeated measures","volume-title":"Res Square","author":"Peddada","year":"2023"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e01039-23","DOI":"10.1128\/msystems.01039-23","article-title":"Species-level resolution for the vaginal microbiota with short amplicons","volume":"9","author":"Qing","year":"2024","journal-title":"mSystems"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1093\/cid\/ciaf673","article-title":"State-of-the-art review: managing vulvovaginal candidiasis","volume":"82","author":"Rautemaa-Richardson","year":"2026","journal-title":"Clin. Infect. Dis."},{"key":"ref31","doi-asserted-by":"publisher","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."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"460","DOI":"10.12688\/f1000research.13706.1","article-title":"Has knowledge of the vaginal microbiome altered approaches to health and disease?","volume":"7","author":"Reid","year":"2018","journal-title":"F1000Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.3389\/fmicb.2019.02669","article-title":"A role for yeast\/pseudohyphal cells of Candida albicans in the correlated expression of NLRP3 inflammasome inducers in women with acute vulvovaginal candidiasis","volume":"10","author":"Roselletti","year":"","journal-title":"Front. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"17877","DOI":"10.1038\/s41598-017-17649-8","article-title":"NLRP3 inflammasome is a key player in human vulvovaginal disease caused by Candida albicans","volume":"7","author":"Roselletti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1093\/infdis\/jiz365","article-title":"Vaginal epithelial cells discriminate between yeast and hyphae of Candida albicans in women who are colonized or have vaginal candidiasis","volume":"220","author":"Roselletti","year":"","journal-title":"J. Infect. Dis."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.3390\/microorganisms9122577","article-title":"Lactobacillus iners cell-free supernatant enhances biofilm formation and hyphal\/pseudohyphal growth by Candida albicans vaginal isolates","volume":"9","author":"Sabbatini","year":"2021","journal-title":"Microorganisms"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/sextrans-2018-053949","article-title":"Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines","volume":"96","author":"Sabo","year":"2020","journal-title":"Sex. Transm. Infect."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/S0140-6736(07)60917-9","article-title":"Vulvovaginal candidosis","volume":"369","author":"Sobel","year":"2007","journal-title":"Lancet"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0002-9378(98)80001-X","article-title":"Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations","volume":"178","author":"Sobel","year":"1998","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1111\/j.1600-0463.2007.apm_630.x","article-title":"Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci","volume":"115","author":"Stepanovi\u0107","year":"2007","journal-title":"APMIS"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"471.e1","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":"ref42","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/1471-2180-9-116","article-title":"Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and\/or L. iners are more conducive to the occurrence of abnormal vaginal microflora","volume":"9","author":"Verstraelen","year":"2009","journal-title":"BMC Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e00983","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":"ref44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15698\/mic2020.01.702","article-title":"The role of Lactobacillus species in the control of Candida via biotrophic interactions","volume":"7","author":"Zangl","year":"2020","journal-title":"Microb. Cell"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1480200","DOI":"10.3389\/fcimb.2024.1480200","article-title":"Alterations of the paired maternal vaginal microbiome and neonatal meconium microbiome in vulvovaginal candidiasis positive pregnant women","volume":"14","author":"Zhang","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref46","doi-asserted-by":"crossref","DOI":"10.1101\/857052","article-title":"An optimized 16S rRNA sequencing protocol for vaginal microbiome to avoid biased abundance estimation","author":"Zhang","year":"2019"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"792787","DOI":"10.3389\/fcimb.2021.792787","article-title":"Contribution of Lactobacillus iners to vaginal health and diseases: a systematic review","volume":"11","author":"Zheng","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1128\/IAI.00436-09","article-title":"Vaginal microbiota of women with frequent vulvovaginal candidiasis","volume":"77","author":"Zhou","year":"2009","journal-title":"Infect. Immun."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1939688\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:42:57Z","timestamp":1788417777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1939688\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":48,"alternative-id":["10.3389\/fmicb.2026.1939688"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1939688","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1939688"}}