{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:12:15Z","timestamp":1785888735950,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013596","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82020108032"],"award-info":[{"award-number":["82020108032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472307"],"award-info":[{"award-number":["82472307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173867"],"award-info":[{"award-number":["82173867"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2022YFC2303004"],"award-info":[{"award-number":["2022YFC2303004"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFC2300404"],"award-info":[{"award-number":["2021YFC2300404"]}]},{"name":"Natural Science Foundation of Shanghai","award":["24ZR1480100"],"award-info":[{"award-number":["24ZR1480100"]}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["202101070007E00094"],"award-info":[{"award-number":["202101070007E00094"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Intestinal\n                    <jats:italic>Candida<\/jats:italic>\n                    overgrowth is the major cause of candidemia in intensive care patients. The lack of phytogenic bioactive components in parenteral nutrition inspired us to focus on the role of polyphenols in preventing intestinal\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    overgrowth. Here, we found that tannic acid (TA), which is abundant in tea, coffee, fruit and vegetables, promoted the clearance of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    from feces and increased the survival rate of mice by about 60%. Interestingly, an opposite mechanism of TA-induced hyphal aggregation was observed. The main target of TA was identified as chitosan, which constitutes less than 5\u2030 of the dry weight of the cell wall. The combination of TA and chitosan effectively reduces the invasion and cytotoxicity of\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    hyphae on host cells. As a previously neglected component, chitosan is mainly produced by the chitin deacetylase Cda2. Our results elucidate the essential role of Cda2 in modulating chitin and chitosan levels, as well as in maintaining the stress responses and virulence in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    , suggesting its potential as a target for new antifungal therapies. The protective role of TA indicates that a plant-based diet is critical for intestinal defense against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    pathogenesis, which may develop into new strategies to prevent candidemia.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013596","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:45:24Z","timestamp":1760550324000},"page":"e1013596","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dietary tannic acid promotes intestinal clearance of C. albicans by cross-linking hyphal chitosan"],"prefix":"10.1371","volume":"21","author":[{"given":"Jia","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruina","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2045-6091","authenticated-orcid":true,"given":"Quanzhen","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"issue":"7","key":"ppat.1013596.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"DW Denning","year":"2024","journal-title":"Lancet Infect Dis"},{"issue":"7","key":"ppat.1013596.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009710","article-title":"Candida albicans colonization of the gastrointestinal tract: a double-edged sword","volume":"17","author":"R Alonso-Monge","year":"2021","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013596.ref003","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41591-019-0709-7","article-title":"High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis","volume":"26","author":"B Zhai","year":"2020","journal-title":"Nat Med"},{"issue":"11","key":"ppat.1013596.ref004","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41575-023-00816-w","article-title":"Commensal fungi in intestinal health and disease","volume":"20","author":"KS Ost","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"11","key":"ppat.1013596.ref005","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1038\/s41590-023-01637-4","article-title":"Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19","volume":"24","author":"T Kusakabe","year":"2023","journal-title":"Nat Immunol"},{"key":"ppat.1013596.ref006","doi-asserted-by":"crossref","first-page":"101190","DOI":"10.1016\/j.mam.2023.101190","article-title":"Antifungal prophylaxis and pre-emptive therapy: when and how?","volume":"92","author":"R Sprute","year":"2023","journal-title":"Mol Aspects Med"},{"issue":"2","key":"ppat.1013596.ref007","doi-asserted-by":"crossref","first-page":"2287618","DOI":"10.1080\/19490976.2023.2287618","article-title":"Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response","volume":"15","author":"M Delavy","year":"2023","journal-title":"Gut Microbes"},{"issue":"10","key":"ppat.1013596.ref008","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.chom.2024.09.010","article-title":"Intestinal fungal-host interactions in promoting and maintaining health","volume":"32","author":"JH Hill","year":"2024","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1013596.ref009","doi-asserted-by":"crossref","first-page":"90","DOI":"10.2174\/1389557520666200628032116","article-title":"Herbal extracts with antifungal activity against Candida albicans: a systematic review","volume":"21","author":"H Hsu","year":"2021","journal-title":"Mini Rev Med Chem"},{"issue":"4","key":"ppat.1013596.ref010","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/10408398.2020.1744512","article-title":"Dietary polyphenol impact on gut health and microbiota","volume":"61","author":"MLY Wan","year":"2021","journal-title":"Crit Rev Food Sci Nutr"},{"issue":"6","key":"ppat.1013596.ref011","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3390\/pharmaceutics16060718","article-title":"Antimicrobial activities of natural bioactive polyphenols","volume":"16","author":"MK Mandal","year":"2024","journal-title":"Pharmaceutics"},{"issue":"4","key":"ppat.1013596.ref012","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.mib.2010.05.002","article-title":"Chitin synthesis and fungal pathogenesis","volume":"13","author":"MD Lenardon","year":"2010","journal-title":"Curr Opin Microbiol"},{"issue":"11","key":"ppat.1013596.ref013","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41477-019-0527-4","article-title":"Deacetylation of chitin oligomers increases virulence in soil-borne fungal pathogens","volume":"5","author":"F Gao","year":"2019","journal-title":"Nat Plants"},{"key":"ppat.1013596.ref014","doi-asserted-by":"crossref","first-page":"135645","DOI":"10.1016\/j.foodchem.2023.135645","article-title":"Biological and pharmacological aspects of tannins and potential biotechnological applications","volume":"414","author":"LFM de Melo","year":"2023","journal-title":"Food Chem"},{"issue":"10","key":"ppat.1013596.ref015","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nri.2016.88","article-title":"Immunological aspects of intestinal mucus and mucins","volume":"16","author":"MEV Johansson","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"ppat.1013596.ref016","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ijbiomac.2019.06.102","article-title":"Effect of divalent cations on bovine serum albumin (BSA) and tannic acid interaction and its influence on turbidity and in vitro protein digestibility","volume":"136","author":"E Kaspchak","year":"2019","journal-title":"Int J Biol Macromol"},{"key":"ppat.1013596.ref017","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.reactfunctpolym.2018.12.005","article-title":"Free radical-mediated conjugation of chitosan with tannic acid: characterization and antioxidant capacity","volume":"135","author":"Y Jing","year":"2019","journal-title":"React Funct Polym"},{"key":"ppat.1013596.ref018","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.chemphys.2018.12.009","article-title":"The interaction between chitosan and tannic acid calculated based on the density functional theory","volume":"520","author":"X An","year":"2019","journal-title":"Chem Phys"},{"issue":"2","key":"ppat.1013596.ref019","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00080-21","article-title":"A conserved machinery underlies the synthesis of a Chitosan layer in the Candida chlamydospore cell wall","volume":"6","author":"LD Bemena","year":"2021","journal-title":"mSphere"},{"issue":"5","key":"ppat.1013596.ref020","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1128\/EC.00399-06","article-title":"Chitosan, the deacetylated form of chitin, is necessary for cell wall integrity in Cryptococcus neoformans","volume":"6","author":"LG Baker","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"4","key":"ppat.1013596.ref021","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3390\/polym10040352","article-title":"Chitin deacetylases: structures, specificities, and biotech applications","volume":"10","author":"L Grifoll-Romero","year":"2018","journal-title":"Polymers (Basel)"},{"issue":"4","key":"ppat.1013596.ref022","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41579-022-00796-9","article-title":"Architecture of the dynamic fungal cell wall","volume":"21","author":"NAR Gow","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"24","key":"ppat.1013596.ref023","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.258889","article-title":"Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans","volume":"134","author":"A da Silva Dantas","year":"2021","journal-title":"J Cell Sci"},{"key":"ppat.1013596.ref024","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.3389\/fmicb.2017.02238","article-title":"Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans","volume":"8","author":"D Malavia","year":"2017","journal-title":"Front Microbiol"},{"issue":"6","key":"ppat.1013596.ref025","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3390\/microorganisms9061161","article-title":"Cell wall proteome profiling of a Candida albicans fluconazole-resistant strain from a Lebanese Hospital patient using tandem mass spectrometry-a pilot study","volume":"9","author":"A Awad","year":"2021","journal-title":"Microorganisms"},{"issue":"6","key":"ppat.1013596.ref026","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/AAC.43.6.1401","article-title":"In vitro antifungal activity of nikkomycin Z in combination with fluconazole or itraconazole","volume":"43","author":"RK Li","year":"1999","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ppat.1013596.ref027","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/AAC.00683-11","article-title":"Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo","volume":"56","author":"KK Lee","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ppat.1013596.ref028","doi-asserted-by":"crossref","first-page":"2154548","DOI":"10.1080\/19490976.2022.2154548","article-title":"From intestinal colonization to systemic infections: Candida albicans translocation and dissemination","volume":"14","author":"JL Sprague","year":"2022","journal-title":"Gut Microbes"},{"issue":"11","key":"ppat.1013596.ref029","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1007\/s00134-020-06240-x","article-title":"Invasive candidiasis in critical care: challenges and future directions","volume":"46","author":"C Logan","year":"2020","journal-title":"Intensive Care Med"},{"issue":"3","key":"ppat.1013596.ref030","first-page":"1548","article-title":"Dysbiosis of intestinal microbiota in critically ill patients and risk of in-hospital mortality","volume":"13","author":"R Wei","year":"2021","journal-title":"Am J Transl Res"},{"key":"ppat.1013596.ref031","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cofs.2021.06.003","article-title":"Berry polyphenols and human health: evidence of antioxidant, anti-inflammatory, microbiota modulation, and cell-protecting effects","volume":"42","author":"N Pap","year":"2021","journal-title":"Curr Opin Food Sci"},{"key":"ppat.1013596.ref032","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/130.8.2073S","article-title":"Dietary intake and bioavailability of polyphenols","volume":"130","author":"A Scalbert","year":"2000","journal-title":"J Nutr"},{"issue":"8","key":"ppat.1013596.ref033","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002533","article-title":"Revised estimates for the number of human and bacteria cells in the body","volume":"14","author":"R Sender","year":"2016","journal-title":"PLoS Biol"},{"key":"ppat.1013596.ref034","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jep.2018.01.008","article-title":"Proanthocyanidin polymeric tannins from Stryphnodendron adstringens are effective against Candida spp. isolates and for vaginal candidiasis treatment","volume":"216","author":"ALD de Freitas","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"ppat.1013596.ref035","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12906-015-0597-4","article-title":"Proanthocyanidins polymeric tannin from Stryphnodendron adstringens are active against Candida albicans biofilms","volume":"15","author":"RLF Luiz","year":"2015","journal-title":"BMC Complement Altern Med"},{"issue":"8004","key":"ppat.1013596.ref036","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41586-024-07142-4","article-title":"The hyphal-specific toxin candidalysin promotes fungal gut commensalism","volume":"627","author":"S-H Liang","year":"2024","journal-title":"Nature"},{"issue":"1","key":"ppat.1013596.ref037","doi-asserted-by":"crossref","DOI":"10.1093\/femsyr\/foaa005","article-title":"Transcriptional control of hyphal morphogenesis in Candida albicans","volume":"20","author":"S Villa","year":"2020","journal-title":"FEMS Yeast Res"},{"issue":"3","key":"ppat.1013596.ref038","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.chom.2019.02.008","article-title":"Candida albicans morphogenesis programs control the balance between gut commensalism and invasive infection","volume":"25","author":"JN Witchley","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"6657","key":"ppat.1013596.ref039","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1126\/science.abq3178","article-title":"Peptide YY: A Paneth cell antimicrobial peptide that maintains Candida gut commensalism","volume":"381","author":"JF Pierre","year":"2023","journal-title":"Science"},{"key":"ppat.1013596.ref040","doi-asserted-by":"crossref","first-page":"113561","DOI":"10.1016\/j.biopha.2022.113561","article-title":"Pharmacological effects and mechanisms of tannic acid","volume":"154","author":"W Jing","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"8","key":"ppat.1013596.ref041","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41579-022-00710-3","article-title":"Evasion of plant immunity by microbial pathogens","volume":"20","author":"Y Wang","year":"2022","journal-title":"Nat Rev Microbiol"},{"issue":"5","key":"ppat.1013596.ref042","article-title":"Chitosan biosynthesis and virulence in the human fungal pathogen Cryptococcus gattii","volume":"4","author":"WC Lam","year":"2019","journal-title":"mSphere"},{"issue":"1","key":"ppat.1013596.ref043","article-title":"Cryptococcus neoformans Chitin synthase 3 plays a critical role in dampening host inflammatory responses","volume":"11","author":"CR Hole","year":"2020","journal-title":"mBio"},{"issue":"1","key":"ppat.1013596.ref044","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1567-1364.2005.00017.x","article-title":"Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity","volume":"6","author":"J Ruiz-Herrera","year":"2006","journal-title":"FEMS Yeast Res"},{"key":"ppat.1013596.ref045","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.3389\/fmicb.2019.02993","article-title":"The fungal cell wall: Candida, Cryptococcus, and Aspergillus species","volume":"10","author":"R Garcia-Rubio","year":"2019","journal-title":"Front Microbiol"},{"issue":"1","key":"ppat.1013596.ref046","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00062-20","article-title":"Nucleotide excision repair protein Rad23 regulates cell virulence independent of Rad4 in Candida albicans","volume":"5","author":"J Feng","year":"2020","journal-title":"mSphere"},{"issue":"5","key":"ppat.1013596.ref047","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1091\/mbc.E19-06-0316","article-title":"Hof1 plays a checkpoint-related role in MMS-induced DNA damage response in Candida albicans","volume":"31","author":"IA Feng","year":"2020","journal-title":"Mol Biol Cell"},{"issue":"1","key":"ppat.1013596.ref048","doi-asserted-by":"crossref","DOI":"10.1002\/cpz1.19","article-title":"Targeted genetic changes in Candida albicans using transient CRISPR\u2010Cas9 expression","volume":"1","author":"MY Huang","year":"2021","journal-title":"Curr Protocols"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013596","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:58:07Z","timestamp":1761155887000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013596"}},"subtitle":[],"editor":[{"given":"Vincent","family":"Bruno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013596","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}