{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:38Z","timestamp":1787029298397,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["107-2313-B-214-002-"],"award-info":[{"award-number":["107-2313-B-214-002-"]}]},{"name":"National Science and Technology Council, Taiwan","award":["ISU-112-01-10A"],"award-info":[{"award-number":["ISU-112-01-10A"]}]},{"name":"I-Shou University","award":["107-2313-B-214-002-"],"award-info":[{"award-number":["107-2313-B-214-002-"]}]},{"name":"I-Shou University","award":["ISU-112-01-10A"],"award-info":[{"award-number":["ISU-112-01-10A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Vulvovaginal candidiasis (VVC) is a common gynecological condition primarily caused by Candida albicans. The excessive use of antifungal drugs has led to increased drug resistance, necessitating the search for alternative therapies. This study investigates the synergistic antifungal effects of cranberry proanthocyanidins (PACs) and probiotics against C. albicans. PACs were prepared at different concentrations (low, medium, high) and tested alone and in combination with multi-strain probiotics, including Lactobacillus rhamnosus and Lactobacillus plantarum. The antifungal activity of their cell-free supernatants (CFS) was also assessed. The results demonstrated that the combination of L. plantarum and medium-concentration PACs (L.p. + PACs M) significantly enhathe inhibitionition of C. albicans compared to individual treatments. In the Vaginal Microbiota Communities Analysis, this condition reduced C. albicans relative abundance to below 0.01%. This study highlights the potential of natural compounds and probiotics as alternative therapeutic strategies for VVC.<\/jats:p>","DOI":"10.3390\/pathogens14040308","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T07:46:50Z","timestamp":1742802410000},"page":"308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic Inhibition of Candida albicans by Cranberry Proanthocyanidins and Probiotics: Novel Strategies for Vulvovaginal Candidiasis Treatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Yu-Ru","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-9479","authenticated-orcid":false,"given":"Jung-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei-Chin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Fen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-134X","authenticated-orcid":false,"given":"Chien-Sen","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung 824005, Taiwan"},{"name":"Institute of Biopharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung 804201, Taiwan"},{"name":"Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 5588585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans Pathogenicity Mechanisms","volume":"4","author":"Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1093\/cid\/ciw038","article-title":"Probiotics as Antifungals in Mucosal Candidiasis","volume":"62","author":"Matsubara","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fanning, S., and Mitchell, A.P. (2012). Fungal Biofilms. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002585"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrmicro2475","article-title":"Genetic Control of Candida albicans Biofilm Development","volume":"9","author":"Finkel","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Uppuluri, P., Chaturvedi, A.K., Srinivasan, A., Banerjee, M., Ramasubramaniam, A.K., K\u00f6hler, J.R., and Lopez-Ribot, J.L. (2010). Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000828"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e02696-21","DOI":"10.1128\/spectrum.02696-21","article-title":"Lactobacillus acidophilus, L. plantarum, L. rhamnosus, and L. reuteri Cell-Free Supernatants Inhibit Candida parapsilosis Pathogenic Potential Upon Infection of Vaginal Epithelial Cells Monolayer and in a Transwell Coculture System In Vitro","volume":"10","author":"Spaggiari","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/MOP.0000000000000060","article-title":"Fluconazole Prophylaxis for Prevention of Invasive Candidiasis in Infants","volume":"26","author":"Ericson","year":"2014","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a019745","DOI":"10.1101\/cshperspect.a019745","article-title":"Antifungal Clinical Trials and Guidelines: What We Know and Do Not Know","volume":"4","author":"Pappas","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/myc.12330","article-title":"Antifungal Drug Resistance Among Candida Species: Mechanisms and Clinical Impact","volume":"58","author":"Sanguinetti","year":"2015","journal-title":"Mycoses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1600-0722.2005.00191.x","article-title":"Probiotics: Do They Have a Role in Oral Medicine and Dentistry?","volume":"113","author":"Meurman","year":"2005","journal-title":"Eur. J. Oral. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1007\/s00253-016-7527-3","article-title":"Probiotic Lactobacilli Inhibit Early Stages of Candida albicans Biofilm Development by Reducing Their Growth, Cell Adhesion, and Filamentation","volume":"100","author":"Matsubara","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kwoji, I.D., Aiyegoro, O.A., Okpeku, M., and Adeleke, M.A. (2021). Multi-Strain Probiotics: Synergy Among Isolates Enhances Biological Activities. Biology, 10.","DOI":"10.3390\/biology10040322"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Superti, F., and De Seta, F. (2020). Warding Off Recurrent Yeast and Bacterial Vaginal Infections: Lactoferrin and Lactobacilli. Microorganisms, 8.","DOI":"10.3390\/microorganisms8010130"},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","first-page":"636474","article-title":"Probiotic Interference of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 with the Opportunistic Fungal Pathogen Candida albicans","volume":"2012","author":"Assefa","year":"2012","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ijfoodmicro.2004.05.012","article-title":"Monostrain, Multistrain, and Multispecies Probiotics\u2014A Comparison of Functionality and Efficacy","volume":"96","author":"Timmerman","year":"2004","journal-title":"Int. J. Food Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/10408390802145377","article-title":"Phytochemicals of Cranberries and Cranberry Products: Characterization, Potential Health Effects, and Processing Stability","volume":"49","author":"Pappas","year":"2009","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/mnfr.200600275","article-title":"A Systematic Review of the Evidence for Cranberries and Blueberries in UTI Prevention","volume":"51","author":"Jepson","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","first-page":"CD001321","article-title":"Cranberries for Preventing Urinary Tract Infections","volume":"10","author":"Jepson","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/2049-632X.12168","article-title":"Promising Results of Cranberry in the Prevention of Oral Candida Biofilms","volume":"70","author":"Girardot","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/jsfa.3966","article-title":"Multi-Laboratory Validation of a Standard Method for Quantifying Proanthocyanidins in Cranberry Powders","volume":"90","author":"Prior","year":"2010","journal-title":"J. Sci. Food Agric."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/j.phytochem.2005.01.008","article-title":"Proanthocyanidin Biosynthesis\u2014Still More Questions than Answers?","volume":"66","author":"Xie","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3109\/13880200490893474","article-title":"Proanthocyanidins: Biological Activities Associated with Human Health","volume":"42","author":"Beecher","year":"2004","journal-title":"Pharm. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"\u00d6zcan, E., Rozycki, M.R., and Sela, D.A. (2021). Cranberry Proanthocyanidins and Dietary Oligosaccharides Synergistically Modulate Lactobacillus plantarum Physiology. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030656"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.14227\/DT180311P15","article-title":"Simulated biological fluids with possible application in dissolution testing","volume":"18","author":"Marques","year":"2011","journal-title":"Dissolution Technol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cao, X.D., Jien, S.H., Yang, C.W., Lin, Y.H., and Liao, C.S. (2024). Innovative Microbial Immobilization Strategy for Di-n-Butyl Phthalate Biodegradation Using Biochar-Calcium Alginate-Waterborne Polyurethane Composites. Microorganisms, 12.","DOI":"10.3390\/microorganisms12071265"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, H., Wang, W., Yu, S., Wang, H., Tian, Z., and Zhu, S. (2022). Procyanidins and Their Therapeutic Potential Against Oral Diseases. Molecules, 27.","DOI":"10.3390\/molecules27092932"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, D., Hwang, G., Liu, Y., Wang, Y., Singh, A.P., Vorsa, N., and Koo, H. (2015). Cranberry Flavonoids Modulate Cariogenic Properties of Mixed-Species Biofilm Through Exopolysaccharides-Matrix Disruption. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145844"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/4\/308\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:59:10Z","timestamp":1760029150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/4\/308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["pathogens14040308"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14040308","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]}}}