{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:11:13Z","timestamp":1792069873451,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both are considered independent and caused by unrelated pathogenic mechanisms. Clinical experience, however, is strongly suggestive that in some populations these infections are linked with recurrent BV (RBV) serving as the dominant etiopathogenic trigger for development of recurrent VVC (RVVC) with profound clinical and therapeutic consequences. The biologic basis for this critical interrelationship is discussed and suggests that as a consequence of BV dysbiosis, and not necessarily because of antibiotics prescribed, immune defenses are compromised, neutralizing vaginal yeast tolerance. The consequent BV-induced vaginal proinflammatory environment predisposes to mixed infection or consecutive episodes of post-treatment VVC. Recurrent BV and repeated antimicrobial drug exposure also predispose to acquired fluconazole resistance in C. albicans isolates, contributing to refractory vulvovaginal candidiasis.<\/jats:p>","DOI":"10.3390\/microorganisms12010108","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T03:43:00Z","timestamp":1704426180000},"page":"108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Bacterial Vaginosis and Vulvovaginal Candidiasis Pathophysiologic Interrelationship"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-4609","authenticated-orcid":false,"given":"Jack D.","family":"Sobel","sequence":"first","affiliation":[{"name":"C.S. Mott Center for Growth and Human Development, 275 E. Hancock St, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-4012","authenticated-orcid":false,"given":"Yogitha Sai","family":"Vempati","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.riam.2021.03.002","article-title":"Chronic recurrent vulvovaginitis is not only due to Candida","volume":"38","author":"Arechavala","year":"2021","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00487-20","DOI":"10.1128\/IAI.00487-20","article-title":"The Complex Link between the Female Genital Microbiota, Genital Infections, and Inflammation","volume":"89","author":"Dabee","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1111\/jog.15267","article-title":"Vulvovaginal candidiasis: An overview of mycological, clinical, and immunological aspects","volume":"48","author":"Jafarzadeh","year":"2022","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kalia, N., Singh, J., and Kaur, M. (2020). Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: A critical review. Ann. Clin. Microbiol. Antimicrob., 19.","DOI":"10.1186\/s12941-020-0347-4"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Louren\u00e7o, A., Pedro, N.A., Salazar, S.B., and Mira, N.P. (2019). Effect of Acetic Acid and Lactic Acid at Low pH in Growth and Azole Resistance of Candida albicans and Candida glabrata. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.03265"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bojang, E., Ghuman, H., Kumwenda, P., and Hall, R.A. (2021). Immune Sensing of Candida albicans. J. Fungi, 7.","DOI":"10.3390\/jof7020119"},{"key":"ref_7","first-page":"ftx096","article-title":"Contribution of TLR2 pathway in the pathogenesis of vulvovaginal candidiasis","volume":"75","author":"Vigezzi","year":"2017","journal-title":"Pathog. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Balakrishnan, S.N., Yamang, H., Lorenz, M.C., Chew, S.Y., and Than, L.T.L. (2022). Role of Vaginal Mucosa, Host Immunity and Microbiota in Vulvovaginal Candidiasis. Pathogens, 11.","DOI":"10.3390\/pathogens11060618"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Willems, H.M.E., Ahmed, S.S., Liu, J., Xu, Z., and Peters, B.M. (2020). Vulvovaginal Candidiasis: A Current Understanding and Burning Questions. J. Fungi, 6.","DOI":"10.3390\/jof6010027"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gaziano, R., Sabbatini, S., and Monari, C. (2023). The interplay between Candida albicans, vaginal mucosa, host immunity and resident microbiota in health and disease: An overview and future perspective. Microorganisms, 11.","DOI":"10.3390\/microorganisms11051211"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e0106621","DOI":"10.1128\/mSystems.01066-21","article-title":"A Complex Microbial Interplay Underlies Recurrent Vulvovaginal Candidiasis Pathobiology","volume":"6","author":"Papon","year":"2021","journal-title":"mSystems"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rosati, D., Bruno, M., Jaeger, M., Ten Oever, J., and Netea, M.G. (2020). Recurrent Vulvovaginal Candidiasis: An Immunological Perspective. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020144"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ardizzoni, A., Wheeler, R.T., and Pericolini, E. (2021). It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.692491"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Parolin, C., Marangoni, A., Laghi, L., Foschi, C., \u00d1ahui Palomino, R.A., Calonghi, N., Cevenini, R., and Vitali, B. (2015). Isolation of Vaginal Lactobacilli and Characterization of Anti-Candida Activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131220"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/emmm.201201678","article-title":"Genetic susceptibility to Candida infections","volume":"5","author":"Smeekens","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/aid.2018.0304","article-title":"The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission","volume":"35","author":"McKinnon","year":"2019","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1128\/JCM.01272-07","article-title":"Targeted PCR for detection of vaginal bacteria associated with bacterial vaginosis","volume":"45","author":"Fredricks","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vodstrcil, L.A., Muzny, C.A., Plummer, E.L., Sobel, J.D., and Bradshaw, C.S. (2021). Bacterial vaginosis: Drivers of recurrence and challenges and opportunities in partner treatment. BMC Med., 19.","DOI":"10.1186\/s12916-021-02077-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1097\/01.AOG.0000183594.45524.d2","article-title":"Adherent biofilms in bacterial vaginosis","volume":"106","author":"Swidsinski","year":"2005","journal-title":"Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1093\/infdis\/jiw140","article-title":"The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes","volume":"214","author":"Murphy","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chacra, L.A., Fenollar, F., and Diop, K. (2022). Bacterial Vaginosis: What Do We Currently Know?. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.672429"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1128\/AEM.01251-07","article-title":"Dynamics of vaginal bacterial communities in women developing bacterial vaginosis, candidiasis, or no infection, analyzed by PCR-denaturing gradient gel electrophoresis and real-time PCR","volume":"73","author":"Vitali","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/QCO.0000000000000620","article-title":"Host\u2013vaginal microbiota interactions in the pathogenesis of bacterial vaginosis","volume":"33","author":"Muzny","year":"2020","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1600-0463.2005.apm1130201.x","article-title":"Bacterial vaginosis\u2014A microbiological and immunological enigma","volume":"113","author":"Forsum","year":"2005","journal-title":"Apmis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1093\/infdis\/jiz514","article-title":"Interleukin-36\u03b3 Is Elevated in Cervicovaginal Epithelial Cells in Women with Bacterial Vaginosis and In Vitro after Infection with Microbes Associated With Bacterial Vaginosis","volume":"221","author":"Gardner","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/aji.12264","article-title":"Bacterial vaginosis and the cervicovaginal immune response","volume":"71","author":"Mitchell","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00410-17","DOI":"10.1128\/IAI.00410-17","article-title":"Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females","volume":"86","author":"Lennard","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103599","DOI":"10.1016\/j.micpath.2019.103599","article-title":"Vaginal microbiota of asymptomatic bacterial vaginosis and vulvovaginal candidiasis: Are they different from normal microbiota?","volume":"134","author":"Pramanick","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11908-023-00798-5","article-title":"Lactobacillus iners and genital health: Molecular clues to an enigmatic vaginal species","volume":"25","author":"Holm","year":"2023","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","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":"ref_32","doi-asserted-by":"crossref","first-page":"e0050322","DOI":"10.1128\/iai.00503-22","article-title":"Treatment of Bacterial Infections with \u03b2-Lactams: Cooperation with Innate Immunity","volume":"91","author":"Carnoy","year":"2023","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/OLQ.0000000000001420","article-title":"Recurrent Bacterial Vaginosis: An Unmet Therapeutic Challenge. Experience With a Combination Pharmacotherapy Long-Term Suppressive Regimen","volume":"48","author":"Surapaneni","year":"2021","journal-title":"Sex. Transm. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1128\/JCM.42.11.5170-5175.2004","article-title":"Analysis of vaginal acetic acid in patients undergoing treatment for bacterial vaginosis","volume":"42","author":"Chaudry","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lehtoranta, L., Hibberd, A.A., Yeung, N., Laitila, A., Maukonen, J., and Ouwehand, A.C. (2021). Characterization of vaginal fungal communities in healthy women and women with bacterial vaginosis (BV); a pilot study. Microb. Pathog., 161.","DOI":"10.1016\/j.micpath.2021.105055"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00294-015-0540-8","article-title":"Environmental pH adaption and morphological transitions in Candida albicans","volume":"62","author":"Du","year":"2016","journal-title":"Curr. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4161\/viru.20010","article-title":"Regulation of phenotypic transitions in the fungal pathogen Candida albicans","volume":"3","author":"Huang","year":"2012","journal-title":"Virulence"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1128\/MMBR.00009-06","article-title":"Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans","volume":"71","author":"Biswas","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0002-9378(99)70563-6","article-title":"Is the lack of concurrence of bacterial vaginosis and vaginal candidosis explained by the presence of bacterial amines?","volume":"181","author":"Rodrigues","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, T., Liu, Z., Zhang, X., Chen, X., and Wang, S. (2019). Local Probiotic Lactobacillus crispatus and Lactobacillus delbrueckii Exhibit Strong Antifungal Effects Against Vulvovaginal Candidiasis in a Rat Model. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01033"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"d\u2019Enfert, C., Kaune, A.K., Alaban, L.R., Chakraborty, S., Cole, N., Delavy, M., Kosmala, D., Marsaux, B., Frois-Martins, R., and Morelli, M. (2021). The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: Current knowledge and new perspectives. FEMS Microbiol. Rev., 45.","DOI":"10.1093\/femsre\/fuaa060"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1073\/pnas.1620432114","article-title":"Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans","volume":"114","author":"Graham","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bnfaga, A.A., Lee, K.W., Than, L.T.L., and Amin-Nordin, S. (2023). Antimicrobial and immunoregulatory effects of Lactobacillus delbrueckii 45E against genitourinary pathogens. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00913-7"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/mi.2015.86","article-title":"Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier","volume":"9","author":"Borgdorff","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.immuni.2015.04.019","article-title":"Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract","volume":"42","author":"Byrne","year":"2015","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3389\/fimmu.2014.00386","article-title":"TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens","volume":"5","author":"McClure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sherrington, S.L., Sorsby, E., Mahtey, N., Kumwenda, P., Lenardon, M.D., Brown, I., Ballou, E.R., MacCallum, D.M., and Hall, R.A. (2017). Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006403"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e02347-19","DOI":"10.1128\/mBio.02347-19","article-title":"Remasking of Candida albicans \u03b2-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing","volume":"10","author":"Cottier","year":"2019","journal-title":"mBio"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/OLQ.0000000000001730","article-title":"Vaginal Candida albicans: High Frequency of in Vitro Fluconazole Resistance in a Select Population\u2014A Brief Note","volume":"50","author":"Agrawal","year":"2022","journal-title":"Sex. Transm. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1097\/AOG.0b013e31827307b2","article-title":"Fluconazole-resistant Candida albicans vulvovaginitis","volume":"120","author":"Marchaim","year":"2012","journal-title":"Obstet. Gynecol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/LGT.0000000000000733","article-title":"Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid","volume":"27","author":"File","year":"2023","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/AAC.05947-11","article-title":"Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection","volume":"56","author":"Krieger","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1093\/cid\/ciaa260","article-title":"Diagnosis and Treatment of Vaginal Discharge Syndromes in Community Practice Settings","volume":"72","author":"Hillier","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/1753425909357577","article-title":"Telling apart friend from foe: Discriminating between commensals and pathogens at mucosal sites","volume":"16","author":"Srinivasan","year":"2010","journal-title":"Innate Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1093\/infdis\/jiaa444","article-title":"An Exaggerated Monocyte-Derived Cytokine Response to Candida Hyphae in Patients with Recurrent Vulvovaginal Candidiasis","volume":"225","author":"Rosati","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1056\/NEJMoa033114","article-title":"Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis","volume":"351","author":"Sobel","year":"2004","journal-title":"N. Engl. J. Med."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/1\/108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:40:20Z","timestamp":1760103620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/1\/108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["microorganisms12010108"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12010108","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,5]]}}}