{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T19:21:20Z","timestamp":1772652080754,"version":"3.50.1"},"reference-count":47,"publisher":"Institute of Biochemistry","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BIOMED KHIM"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Recurrent vulvovaginal candidiasis (RVVC) is one of the most complex forms of urogenital infection in terms of its clinical burden, impact on quality of life, and difficulty in preventing relapses. The aim of this study was to comprehensively characterize the taxonomic composition and functional potential of the vaginal microbiome associated with RVVC. This case-control study included patients with RVVC and conditionally healthy women. Vaginal samples were analyzed using shotgun metagenomic sequencing, followed by taxonomic and functional annotation of the microbiome using data quality control, taxonomic classification (Kraken2, MetaPhlAn4), and functional annotation (HUMAnN 3.9). At the community structure level, the RVVC microbiome exhibited pronounced interindividual variability and did not represent a uniform microbiota configuration. The taxonomic profile of the microbiome in RVVC was characterized by an increased relative abundance of Lactobacillus iners and anaerobic taxa (Prevotella bivia, Dialister microaerophilus), forming a compact \u201ccore\u201d of intergroup differences. Functional analysis revealed a limited but reproducible set of metabolic pathways associated with RVVC; these included pathways of purine metabolism, central carbohydrate metabolism, and biosynthesis of cofactors and cell wall components. RVVC is associated not only with changes in the taxonomic composition of the microbiota but also with a stable reconfiguration of its functional potential. The identified shifts in metabolic pathway patterns reflect a transition of the vaginal microbial community to an alternative functional state, thus highlighting the need to develop new therapeutic strategies alternative to traditional antifungal-based approaches.<\/jats:p>","DOI":"10.18097\/pbmcr1644","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:51:32Z","timestamp":1772646692000},"page":"62-74","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome associated with recurrent vulvovaginal candidiasis: key characteristics and potential therapeutic targets"],"prefix":"10.18097","volume":"72","author":[{"given":"E.G.","family":"Oganesyan","sequence":"first","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.S.","family":"Zhuk","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia; Institute of Applied Computer Science, ITMO University, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.V.","family":"Venchakova","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu.V.","family":"Dolgo-Saburova","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.N.","family":"Zhorzh","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.-M.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.V.","family":"Vasilyeva","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.E.","family":"Taraskina","sequence":"additional","affiliation":[{"name":"Kashkin Research Institute of Medical Mycology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7443","published-online":{"date-parts":[[2026]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Caetano C.F., Gaspar C., Martinez-de-Oliveira J., Palmeira-de-Oliveira A., Rolo J. (2023) The role of yeasts in human health: a review. Life, 13(4), 924.","DOI":"10.3390\/life13040924"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Esposito M.M., Patsakos S., Borruso L. (2023) The role of the mycobiome in women\u2019s health. J. Fungi, 9(3), 348.","DOI":"10.3390\/jof9030348"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Moosa Y., Kwon D., de Oliveira T., Wong E.B. (2020) Determinants of vaginal microbiota composition. Front. Cell. Infect. Microbiol., 10, 467.","DOI":"10.3389\/fcimb.2020.00467"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z., Li F., Yu X., Feng Q., Wang Z., Xie H., Chen X., Zeng C., Wen B., Zeng L., Du H., Tang H., Xu C., Xia Y., Xia H., Yang H., Wang J., Wang J., Madsen L., Brix S., Kristiansen K., Xu X., Li J., Wu R., Jia H. (2017) The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun., 8, 875.","DOI":"10.1038\/s41467-017-00901-0"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Son K.-A., Kim M., Kim Y.M., Kim S.H., Choi S.-J., Oh S.-Y., Roh C.-R., Kim J.-H. (2018) Prevalence of vaginal microorganisms among pregnant women according to trimester and association with preterm birth. Obstet. Gynecol. Sci., 61(1), 38\u201347.","DOI":"10.5468\/ogs.2018.61.1.38"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Fettweis J.M., Serrano M.G., Brooks J.P., Edwards D.J., Girerd P.H., Parikh H.I., Huang B., Arodz T.J., Edupuganti L., Glascock A.L., Xu J., Jimenez N.R., Vivadelli S.C., Fong S.S., Sheth N.U., Jean S., Lee V., Bokhari Y.A., Lara A.M., Mistry S.D., Duckworth R.A. 3rd, Bradley S.P., Koparde V.N., Orenda X.V., Milton S.H., Rozycki S.K., Matveyev A.V., Wright M.L., Huzurbazar S.V., Jackson E.M., Smirnova E., Korlach J., Tsai Y.C., Dickinson M.R., Brooks J.L., Drake J.I., Chaffin D.O., Sexton A.L., Gravett M.G., Rubens C.E., Wijesooriya N.R., Hendricks-Mu\u00f1oz K.D., Jefferson K.K., Strauss J.F. 3rd, Buck G.A. (2019) The vaginal microbiome and preterm birth. Nat. Med., 25(6), 1012\u20131021.","DOI":"10.1038\/s41591-019-0450-2"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Chee W.J.Y., Chew S.Y., Than L.T.L. (2020) Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb. Cell Fact., 19(1), 203.","DOI":"10.1186\/s12934-020-01464-4"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Bradshaw C.S., Sobel J.D. (2016) Current treatment of bacterial vaginosis \u2014 limitations and need for innovation. J. Infect. Dis., 214(Suppl 1), S14\u2013S20.","DOI":"10.1093\/infdis\/jiw159"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Younes J.A., Lievens E., Hummelen R., van der Westen R., Reid G., Petrova M.I. (2018) Women and their microbes: the unexpected friendship. Trends Microbiol., 26(1), 16\u201332.","DOI":"10.1016\/j.tim.2017.07.008"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Bradfield Strydom M., Khan S., Walpola R.L., Ware R.S., Tiralongo E. (2023) Interplay of the microbiome and antifungal therapy in recurrent vulvovaginal candidiasis (RVVC): a narrative review. J. Med. Microbiol., 72(5), 001705.","DOI":"10.1099\/jmm.0.001705"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Alonso-Roman R., Last A., Mirhakkak M.H., Sprague J.L., M\u00f6ller L., Gro\u00dfmann P., Graf K., Gratz R., Mogavero S., Vylkova S., Panagiotou G., Sch\u00e4uble S., Hube B., Gresnigt M.S. (2022) Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nat. Commun., 13, 3192.","DOI":"10.1038\/s41467-022-30661-5"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Hasselrot T., Alvendal C., Hunt S., Franz\u00e9n Boger M., Kaldhusdal V., Damdimopoulos A., Schuppe-Koistinen I., Edfeldt G., Bohm-Starke N., Broliden K. (2025) Vaginal transcriptional signatures of the neutrophil-driven immune response correlate with clinical severity during recurrent vulvovaginal candidiasis. Am. J. Reprod. Immunol., 93(1), e70040.","DOI":"10.1111\/aji.70040"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"McKloud E., Delaney C., Sherry L., Kean R., Williams S., Metcalfe R., Thomas R., Richardson R., Gerasimidis K., Nile C.J., Williams C., Ramage G. (2021) Recurrent vulvovaginal candidiasis: a dynamic interkingdom biofilm disease of Candida and Lactobacillus. mSystems, 6(4), e00622-21.","DOI":"10.1128\/mSystems.00622-21"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Patel D.A., Gillespie B., Sobel J.D., Leaman D., Nyirjesy P., Weitz M.V., Foxman B. (2004) Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am. J. Obstet. Gynecol., 190(3), 644\u2013653.","DOI":"10.1016\/j.ajog.2003.11.027"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Sobel J.D. (2007) Vulvovaginal candidosis. Lancet, 369(9577), 1961\u20131971.","DOI":"10.1016\/S0140-6736(07)60917-9"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Denning D.W., Kneale M., Sobel J.D., Rautemaa-Richardson R. (2018) Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect. Dis., 18(11), e339\u2013e347.","DOI":"10.1016\/S1473-3099(18)30103-8"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Yano J., Sobel J.D., Nyirjesy P., Sobel R., Williams V.L., Yu Q., Noverr M.C., Holland M.J., Fidel P.L. Jr (2019) Current patient perspectives of vulvovaginal candidiasis. BMC Women\u2019s Health, 19, 48.","DOI":"10.1186\/s12905-019-0748-8"},{"key":"ref18","unstructured":"Cornely O.A. (2021) Global guideline for the diagnosis and management of candidiasis [Internet]. ECMM\/ISHAM. Retrieved January 3, 2026, from: https:\/\/www.ecmm.info\/guidelines\/."},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Arastehfar A., Kargar M.L., Mohammadi S.R., Roudbary M., Ghods N., Haghighi L., Daneshnia F., Tavakoli M., Jafarzadeh J., Hedayati M.T., Wang H., Fang W., Carvalho A., Ilkit M., Perlin D.S., Lass-Fl\u00f6rl C. (2021) A high rate of recurrent vulvovaginal candidiasis and therapeutic failure of azole derivatives among Iranian women. Front. Microbiol., 12, 655069.","DOI":"10.3389\/fmicb.2021.655069"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Zhou X., Westman R., Hickey R., Hansmann M.A., Kennedy C., Osborn T.W., Forney L.J. (2009) Vaginal microbiota of women with frequent vulvovaginal candidiasis. Infect. Immun., 77(9), 4130\u20134135.","DOI":"10.1128\/IAI.00436-09"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Macklaim J.M., Clemente J.C., Knight R., Gloor G.B., Reid G. (2015) Changes in vaginal microbiota following antimicrobial and probiotic therapy. Microb. Ecol. Health Dis., 26, 27799.","DOI":"10.3402\/mehd.v26.27799"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Tortelli B.A., Lewis W.G., Allsworth J.E., Member-Meneh N., Foster L.R., Reno H.E., Peipert J.F., Fay J.C., Lewis A.L. (2020) Associations between the vaginal microbiome and Candida colonization in women of reproductive age. Am. J. Obstet. Gynecol., 222(5), 471.e1\u2013471.e9.","DOI":"10.1016\/j.ajog.2019.10.008"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Petrova M.I., Reid G., Vaneechoutte M., Lebeer S. (2017) Lactobacillus iners: friend or foe? Trends Microbiol., 25(3), 182\u2013191.","DOI":"10.1016\/j.tim.2016.11.007"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Delavy M., Sertour N., d\u2019Enfert C., Bougnoux M.-E. (2023) Metagenomics and metabolomics approaches in the study of Candida albicans colonization of host niches. Trends Microbiol., 31(12), 1276\u20131286.","DOI":"10.1016\/j.tim.2023.08.002"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Quince C., Walker A.W., Simpson J.T., Loman N.J., Segata N. (2017) Shotgun metagenomics, from sampling to analysis. Nat. Biotechnol., 35(9), 833\u2013844.","DOI":"10.1038\/nbt.3935"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Liang Y., Huang Z., Fan S., Li C., Huang L., Huang C., Hutchins A.P., Fang C., Zhang X. (2024) Highlight signatures of vaginal microbiota and metabolome contributed to the occurrence and recurrence of vulvovaginal candidiasis. Microbiol. Spectr., 12(12), e01521-24.","DOI":"10.1128\/spectrum.01521-24"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Hameed S., Hans S., Monasky R., Thangamani S., Fatima Z. (2021) Understanding human microbiota offers novel and promising therapeutic options against Candida infections. Pathogens, 10(2), 183.","DOI":"10.3390\/pathogens10020183"},{"key":"ref28","unstructured":"Babraham Bioinformatics, Babraham Institute, Cambridge, UK. Retrieved January 22, 2026, from: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Chen S., Zhou Y., Chen Y., Gu J. (2018) fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics, 34(17), i884\u2013i890.","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Liu Y.-X., Qin Y., Chen T., Lu M., Qian X., Guo X., Bai Y. (2021) A practical guide to amplicon and metagenomic analysis of microbiome data. Protein Cell, 12(5), 315\u2013330.","DOI":"10.1007\/s13238-020-00724-8"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Wood D.E., Lu J., Langmead B. (2019) Improved metagenomic analysis with Kraken 2. Genome Biol., 20, 257.","DOI":"10.1186\/s13059-019-1891-0"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Blanco-M\u00edguez A., Beghini F., Cumbo F., McIver L.J., Thompson K.N., Zolfo M., Manghi P., Dubois L., Huang K.D., Thomas A.M., Nickols W.A., Piccinno G., Piperni E., Pun\u010doch\u00e1\u0159 M., Valles-Colomer M., Tett A., Giordano F., Davies R., Wolf J., Berry S.E., Spector T.D., Franzosa E.A., Pasolli E., Asnicar F., Huttenhower C., Segata N. (2023) Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4. Nat. Biotechnol., 41(11), 1633\u20131644.","DOI":"10.1038\/s41587-023-01688-w"},{"key":"ref33","unstructured":"humann3 \u2013 The Huttenhower Lab. Retrieved January 11, 2026, from: https:\/\/huttenhower.sph.harvard.edu\/humann\/."},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Lee C.Y., Diegel J., France M.T., Ravel J., Arnold K.B. (2023) Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy. PLOS Comput. Biol., 19(8), e1011295.","DOI":"10.1371\/journal.pcbi.1011295"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Vaneechoutte M. (2017) Lactobacillus iners, the unusual suspect. Res. Microbiol., 168(9\u201310), 826\u2013836.","DOI":"10.1016\/j.resmic.2017.09.003"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Cohen S., Ost K.S., Doran K.S. (2024) Impact of interkingdom microbial interactions in the vaginal tract. PLOS Pathogens, 20(3), e1012018.","DOI":"10.1371\/journal.ppat.1012018"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Muzny C.A., Elnaggar J.H., Sousa L.G.V., Lima \u00c2., Aaron K.J., Eastlund I.C., Graves K.J., Dong C., van Gerwen O.T., Luo M., Tamhane A., Long D., Cerca N., Taylor C.M. (2024) Microbial interactions among Gardnerella, Prevotella and Fannyhessea prior to incident bacterial vaginosis: protocol for a prospective, observational study. BMJ Open, 14(2), e083516.","DOI":"10.1136\/bmjopen-2023-083516"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"MacAlpine J., Lionakis M.S. (2024) Host-microbe interaction paradigms in acute and recurrent vulvovaginal candidiasis. Cell Host Microbe, 32(10), 1654\u20131667.","DOI":"10.1016\/j.chom.2024.08.018"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Pietrella D., Rachini A., Pines M., Pandey N., Mosci P., Bistoni F., d\u2019Enfert C., Vecchiarelli A. (2011) Th17 cells and IL-17 in protective immunity to vaginal candidiasis. PLOS One, 6(7), e22770.","DOI":"10.1371\/journal.pone.0022770"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Borghi M., de Luca A., Puccetti M., Jaeger M., Mencacci A., Oikonomou V., Pariano M., Garlanda C., Moretti S., Bartoli A., Sobel J., van de Veerdonk F.L., Dinarello C.A., Netea M.G., Romani L. (2015) Pathogenic NLRP3 inflammasome activity during Candida infection is negatively regulated by IL-22 via activation of NLRC4 and IL-1Ra. Cell Host Microbe, 18(2), 198\u2013209.","DOI":"10.1016\/j.chom.2015.07.004"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Camilli G., Griffiths J.S., Ho J., Richardson J.P., Naglik J.R. (2020) Some like it hot: Candida activation of inflammasomes. PLOS Pathogens, 16(10), e1008975.","DOI":"10.1371\/journal.ppat.1008975"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"France M.T., Fu L., Rutt L., Yang H., Humphrys M.S., Narina S., Gajer P., Ma B., Forney L.J., Ravel J. (2022) Insight into the ecology of vaginal bacteria through integrative analyses of metagenomic and metatranscriptomic data. Genome Biol., 23, 66.","DOI":"10.1186\/s13059-022-02635-9"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Miller E.A., Beasley D.E., Dunn R.R., Archie E.A. (2016) Lactobacilli dominance and vaginal pH: why is the human vaginal microbiome unique? Front. Microbiol., 7, 1936.","DOI":"10.3389\/fmicb.2016.01936"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"van der Veer C., Hertzberger R.Y., Bruisten S.M., Tytgat H.L.P., Swanenburg J., de Kat Angelino-Bart A., Schuren F., Molenaar D., Reid G., de Vries H., Kort R. (2019) Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota. Microbiome, 7, 49.","DOI":"10.1186\/s40168-019-0667-9"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Song J., Dong X., Lan Y., Lu Y., Liu X., Kang X., Huang Z., Yue B., Liu Y., Ma W., Zhang L., Yan H., He M., Fan Z., Guo T. (2024) Interpretation of vaginal metagenomic characteristics in different types of vaginitis. mSystems, 9(3), e01377\u201323.","DOI":"10.1128\/msystems.01377-23"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Bommana S., Richards G., Kama M., Kodimerla R., Jijakli K., Read T.D., Dean D. (2022) Metagenomic shotgun sequencing of endocervical, vaginal, and rectal samples among Fijian women with and without Chlamydia trachomatis reveals disparate microbial populations and function across anatomic sites: a pilot study. Microbiol. Spectr., 10(3), e00105\u201322.","DOI":"10.1128\/spectrum.00105-22"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Boahen A., Than L.T.L., Loke Y.L., Chew S.Y. (2022) The antibiofilm role of biotics family in vaginal fungal infections. Front. Microbiol., 13, 787119.","DOI":"10.3389\/fmicb.2022.787119"}],"container-title":["Biomeditsinskaya Khimiya"],"original-title":[],"language":"ru","deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:51:42Z","timestamp":1772646702000},"score":1,"resource":{"primary":{"URL":"http:\/\/pbmc.ibmc.msk.ru\/en\/article-en\/PBMC-2026-72-1-62"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026]]},"published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.18097\/pbmcr1644","relation":{},"ISSN":["2310-6905","2310-6972"],"issn-type":[{"value":"2310-6905","type":"electronic"},{"value":"2310-6972","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]}}}