{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:25:56Z","timestamp":1771233956425,"version":"3.50.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"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":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Streptococcus mutans<\/jats:italic> is the most prevalent biofilm-forming pathogen in dental caries, while <jats:italic>Candida albicans<\/jats:italic> is often detected in the presence of <jats:italic>S. mutans<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We aimed to evaluate the anti-caries effect of stevioside in medium trypticase soy broth (TSB) with or without sucrose supplementation compared with the same sweetness sucrose and xylitol in a dual-species model of <jats:italic>S. mutans<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic>, based on planktonic growth, crystal violet assay, acid production, biofilm structural imaging, confocal laser scanning microscopy, and RNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that compared with sucrose, stevioside significantly inhibited planktonic growth and acid production, changed the structure of the mixed biofilm, and reduced the viability of biofilm and the production of extracellular polysaccharides in dual-species biofilm. Through RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway impact analysis showed that stevioside decreased sucrose metabolism and increased galactose and intracellular polysaccharide metabolism in <jats:italic>S. mutans<\/jats:italic>, and decreased genes related to GPI-modified proteins and secreted aspartyl proteinase (SAP) family in <jats:italic>C. albicans<\/jats:italic>. In contrast to xylitol, stevioside also inhibited the transformation of fungal morphology of <jats:italic>C. albicans<\/jats:italic>, which did not form mycelia and thus had reduced pathogenicity. Stevioside revealed a superior suppression of dual-species biofilm formation compared to sucrose and a similar anti-caries effect with xylitol. However, sucrose supplementation diminished the suppression of stevioside on <jats:italic>S. mutans<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study is the first to confirm that stevioside has anticariogenic effects on <jats:italic>S. mutans<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic> in a dual-species biofilm. As a substitute for sucrose, it may help reduce the risk of developing dental caries.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1128668","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T05:32:50Z","timestamp":1680672770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibitory effects of Stevioside on Streptococcus mutans and Candida albicans dual-species biofilm"],"prefix":"10.3389","volume":"14","author":[{"given":"Mingzhu","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziye","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruizhe","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.1128\/aem.70.10.6047-6052.2004","article-title":"Galactose metabolism by Streptococcus mutans","volume":"70","author":"Abranches","year":"2004","journal-title":"Appl. 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Community Dent."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/bioinformatics\/btl140","article-title":"Improved scoring of functional groups from gene expression data by decorrelating GO graph structure","volume":"22","author":"Alexa","year":"2006","journal-title":"Bioinformatics"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"103942","DOI":"10.1016\/j.micpath.2019.103942","article-title":"Polymicrobial interactions involving fungi and their importance for the environment and in human disease","volume":"140","author":"Azzam","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.tim.2016.12.012","article-title":"Ecology of the Oral microbiome: beyond bacteria","volume":"25","author":"Baker","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.mib.2006.10.007","article-title":"Morphogenesis and cell cycle progression in Candida albicans","volume":"9","author":"Berman","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1002\/jobm.201500329","article-title":"Levorotatory carbohydrates and xylitol subdue Streptococcus mutans and Candida albicans adhesion and biofilm formation","volume":"56","author":"Brambilla","year":"2016","journal-title":"J. Basic Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.1128\/jb.00574-10","article-title":"The pdh operon is expressed in a subpopulation of stationary-phase bacteria and is important for survival of sugar-starved Streptococcus mutans","volume":"192","author":"Busuioc","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1093\/femsec\/fiy091","article-title":"Sucrose challenges to Streptococcus mutans biofilms and the curve fitting for the biofilm changes","volume":"94","author":"Cai","year":"2018","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.archoralbio.2018.02.019","article-title":"pH changes of mixed biofilms of Streptococcus mutans and Candida albicans after exposure to sucrose solutions in vitro","volume":"90","author":"Cavazana","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"104886","DOI":"10.1016\/j.archoralbio.2020.104886","article-title":"Inhibitory effects of xylitol and sorbitol on Streptococcus mutans and Candida albicans biofilms are repressed by the presence of sucrose","volume":"119","author":"Chan","year":"2020","journal-title":"Arch. Oral Biol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"636684","DOI":"10.3389\/fmicb.2021.636684","article-title":"The route of sucrose utilization by Streptococcus mutans affects intracellular polysaccharide metabolism","volume":"12","author":"Costa Oliveira","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1177\/0022034519845001","article-title":"The role of exopolysaccharides in Oral biofilms","volume":"98","author":"Cugini","year":"2019","journal-title":"J. Dent. 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Oral Investig."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"10802","DOI":"10.1038\/s41598-021-90198-3","article-title":"Association of Candida albicans and Cbp(+) Streptococcus mutans with early childhood caries recurrence","volume":"11","author":"Garcia","year":"2021","journal-title":"Sci. Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.archoralbio.2013.03.005","article-title":"Cariogenic potential of commercial sweeteners in an experimental biofilm caries model on enamel","volume":"58","author":"Giacaman","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e01012","DOI":"10.1128\/aem.01012-20","article-title":"Effect of Rubusoside, a natural sucrose substitute, on Streptococcus mutans biofilm cariogenic potential and virulence gene expression in vitro","volume":"86","author":"Guan","year":"2020","journal-title":"Appl. Environ. 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Microbiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"19661","DOI":"10.1038\/s41598-020-76744-5","article-title":"Disruption of Streptococcus mutans and Candida albicans synergy by a commensal streptococcus","volume":"10","author":"Huffines","year":"2020","journal-title":"Sci. Rep."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e1006407","DOI":"10.1371\/journal.ppat.1006407","article-title":"Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo","volume":"13","author":"Hwang","year":"2017","journal-title":"PLoS Pathog."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1177\/0022034515592859","article-title":"Binding force dynamics of Streptococcus mutans-glucosyltransferase B to Candida albicans","volume":"94","author":"Hwang","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e1003795","DOI":"10.1371\/journal.ppat.1003795","article-title":"Shaping up for battle: morphological control mechanisms in human fungal pathogens","volume":"9","author":"Kadosh","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/j.1574-6968.2006.00522.x","article-title":"Overlapping substrate specificity for sucrose and maltose of two binding protein-dependent sugar uptake systems in Streptococcus mutans","volume":"266","author":"Kilic","year":"2007","journal-title":"FEMS Microbiol. Lett."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.1128\/aem.01160-15","article-title":"Genetics and physiology of acetate metabolism by the Pta-Ack pathway of Streptococcus mutans","volume":"81","author":"Kim","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"623980","DOI":"10.3389\/fcimb.2020.623980","article-title":"Synergism of Streptococcus mutans and Candida albicans reinforces biofilm maturation and Acidogenicity in saliva: an in vitro study","volume":"10","author":"Kim","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"41332","DOI":"10.1038\/srep41332","article-title":"Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref39","first-page":"87","article-title":"The antimicrobial potential of stevia in an in vitro microbial caries model","volume":"29","author":"Kishta Derani","year":"2016","journal-title":"Am. J. Dent."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1128\/aem.01299-08","article-title":"Structural and molecular basis of the role of starch and sucrose in Streptococcus mutans biofilm development","volume":"75","author":"Klein","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fcimb.2015.00010","article-title":"Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms","volume":"5","author":"Klein","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.3390\/nu9111242","article-title":"Effect of a lactobacillus Salivarius probiotic on a double-species Streptococcus mutans and Candida albicans caries biofilm","volume":"9","author":"Krzy\u015bciak","year":"2017","journal-title":"Nutrients"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1128\/mmbr.00024-07","article-title":"Interspecies interactions within oral microbial communities","volume":"71","author":"Kuramitsu","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.foodchem.2011.11.140","article-title":"Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: a comprehensive review on the biochemical, nutritional and functional aspects","volume":"132","author":"Lemus-Mondaca","year":"2012","journal-title":"Food Chem."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12937-017-0278-x","article-title":"Health outcomes of non-nutritive sweeteners: analysis of the research landscape","volume":"16","author":"Lohner","year":"2017","journal-title":"Nutr. J."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e1003616","DOI":"10.1371\/journal.ppat.1003616","article-title":"Streptococcus mutans, Candida albicans, and the human mouth: a sticky situation","volume":"9","author":"Metwalli","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1177\/0022034519866440","article-title":"Metabolic signaling and spatial interactions in the Oral Polymicrobial community","volume":"98","author":"Miller","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1128\/mmbr.67.3.400-428.2003","article-title":"Candida albicans secreted aspartyl proteinases in virulence and pathogenesis","volume":"67","author":"Naglik","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/nrmicro2313","article-title":"Medically important bacterial-fungal interactions","volume":"8","author":"Peleg","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"17030","DOI":"10.1038\/nrdp.2017.30","article-title":"Dental caries","volume":"3","author":"Pitts","year":"2017","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.fgb.2008.08.003","article-title":"Functional analysis of Candida albicans GPI-anchored proteins: roles in cell wall integrity and caspofungin sensitivity","volume":"45","author":"Plaine","year":"2008","journal-title":"Fungal Genet. Biol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e02247","DOI":"10.1128\/aem.02247-18","article-title":"Glycosyltransferase-mediated biofilm matrix dynamics and virulence of Streptococcus mutans","volume":"85","author":"Rainey","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1159\/000314675","article-title":"Association of oral candidal carriage with dental caries in children","volume":"44","author":"Raja","year":"2010","journal-title":"Caries Res."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jinorgbio.2015.11.014","article-title":"Antimicrobial evaluation of new metallic complexes with xylitol active against P. aeruginosa and C. albicans: MIC determination, post-agent effect and Zn-uptake","volume":"155","author":"Santi","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1080\/00016357.2020.1788721","article-title":"Effects of xylitol and erythritol consumption on mutans streptococci and the oral microbiota: a systematic review","volume":"78","author":"S\u00f6derling","year":"2020","journal-title":"Acta Odontol. Scand."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.tim.2004.05.008","article-title":"The distinct morphogenic states of Candida albicans","volume":"12","author":"Sudbery","year":"2004","journal-title":"Trends Microbiol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1038\/ismej.2014.73","article-title":"Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans","volume":"8","author":"Sztajer","year":"2014","journal-title":"ISME J."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1177\/0022034510379602","article-title":"The role of bacteria in the caries process: ecological perspectives","volume":"90","author":"Takahashi","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"845738","DOI":"10.3389\/fcimb.2022.845738","article-title":"The crosstalk between saliva bacteria and fungi in early childhood caries","volume":"12","author":"Tu","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1177\/00220345950740101101","article-title":"Characterization of glucosyltransferaseB, GtfC, and GtfD in solution and on the surface of hydroxyapatite","volume":"74","author":"Venkitaraman","year":"1995","journal-title":"J. Dent. Res."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: quality control of RNA-seq experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1177\/0022034518790941","article-title":"Association between Oral Candida and Bacteriome in children with severe ECC","volume":"97","author":"Xiao","year":"","journal-title":"J. Dent. Res."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1159\/000481833","article-title":"Candida albicans and early childhood caries: a systematic review and meta-analysis","volume":"52","author":"Xiao","year":"","journal-title":"Caries Res."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2147\/dddt.S230857","article-title":"In vitro antifungal effects of Berberine against Candida spp. in planktonic and biofilm conditions","volume":"14","author":"Xie","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"9967035","DOI":"10.1155\/2021\/9967035","article-title":"The effects of nonnutritive sweeteners on the cariogenic potential of Oral microbiome","volume":"2021","author":"Zhu","year":"2021","journal-title":"Biomed. Res. 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