{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:33:55Z","timestamp":1791491635690,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swanson Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Polyols are widely used as non-cariogenic sweeteners in foods and oral care products, yet their comparative activity against diverse oral microbes and their potential relevance to the oral\u2013systemic axis remain incompletely defined. Here, we performed an in vitro, optical density (OD)-based screening of four polyols\u2014allulose, D-mannose, erythritol, and xylitol\u2014against Streptococcus mutans, Streptococcus anginosus, Candida albicans, and Fusobacterium nucleatum. Cultures were grown with polyols at 1\u201320% (w\/v), and OD600 was recorded at organism-specific endpoints (~24 h). Allulose, erythritol, and xylitol produced strong, concentration-dependent suppression of streptococcal growth at \u22655\u201310%, whereas C. albicans showed minimal changes across the tested range. F. nucleatum was highly sensitive to allulose, D-mannose, and xylitol at \u22655% (reducing OD to \u226413% of the untreated control), while low concentrations of D-mannose and erythritol increased OD beyond that of the control, suggesting species-specific utilization or stress responses. One-way ANOVA with Tukey\u2019s HSD post hoc testing supported significant between-polyol differences for most concentrations in Streptococcus spp. and F. nucleatum. Collectively, these results identify polyol- and taxon-specific growth phenotypes that can inform the formulation of swallow-safe oral hygiene products and motivate follow-up work in polymicrobial biofilm models and clinical studies targeting oral inflammation and downstream systemic risk.<\/jats:p>","DOI":"10.3390\/microorganisms14040884","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:11:18Z","timestamp":1776240678000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Inhibition of Pathogens by Polyols: Optical Density-Based Screening and Implications for the Oral\u2013Systemic Axis"],"prefix":"10.3390","volume":"14","author":[{"given":"Mark","family":"Cannon","sequence":"first","affiliation":[{"name":"Ann and Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-9744","authenticated-orcid":false,"given":"Bradley S.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Earth, Environmental and Planetary Sciences, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2026, February 11). 2024 Oral Health Surveillance Report: Selected Findings, Available online: https:\/\/www.cdc.gov\/oral-health\/php\/2024-oral-health-surveillance-report\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1177\/0022034512457373","article-title":"Prevalence of Periodontitis in Adults in the United States: 2009 and 2010","volume":"91","author":"Eke","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/prd.12145","article-title":"Periodontitis Prevalence in Adults \u226565 Years of Age, in the USA","volume":"72","author":"Eke","year":"2016","journal-title":"Periodontol. 2000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1177\/0895937409335623","article-title":"Xylitol and Its Vehicles for Public Health Needs","volume":"21","author":"Milgrom","year":"2009","journal-title":"Adv. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.14219\/jada.archive.2006.0144","article-title":"The Use of Sorbitol-and Xylitol-Sweetened Chewing Gum in Caries Control","volume":"137","author":"Burt","year":"2006","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4103\/0976-9668.198344","article-title":"Xylitol in preventing dental caries: A systematic review and meta-analyses","volume":"8","author":"Janakiram","year":"2017","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000260156","article-title":"Effect of Xylitol on the Growth and Metabolism of Streptococcus mutans","volume":"9","author":"Knuuttila","year":"1975","journal-title":"Caries Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1177\/0895937409335642","article-title":"Xylitol, Mutans Streptococci, and Dental Plaque","volume":"21","year":"2009","journal-title":"Adv. Dent. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Loimaranta, V., Mazurel, D., Deng, D., and S\u00f6derling, E. (2020). Xylitol and Erythritol Inhibit Real-Time Biofilm Formation of Streptococcus mutans. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01867-8"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000261977","article-title":"Effect of sugar alcohols on the composition and metabolism of a mixed culture of oral bacteria grown in a chemostat","volume":"28","author":"Bradshaw","year":"1994","journal-title":"Caries Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000047444","article-title":"Comparison of Erythritol and Xylitol Saliva Stimulants in the Control of Dental Plaque and Mutans Streptococci","volume":"35","author":"Isotupa","year":"2001","journal-title":"Caries Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000084800","article-title":"Similarity of the Effects of Erythritol and Xylitol on Some Risk Factors of Dental Caries","volume":"39","author":"Saag","year":"2005","journal-title":"Caries Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6297","DOI":"10.1038\/s41598-020-63153-x","article-title":"Exploration of Singular and Synergistic Effect of Xylitol and Erythritol on Causative Agents of Dental Caries","volume":"10","author":"Smidt","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Salli, K., Lehtinen, M.J., Tiihonen, K., and Ouwehand, A.C. (2019). Xylitol\u2019s Health Benefits beyond Dental Health: A Comprehensive Review. Nutrients, 11.","DOI":"10.3390\/nu11081813"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2621.1980.tb02616.x","article-title":"A quantitative study of mannitol, sorbitol, xylitol, and xylose in wild berries and commercial fruits","volume":"45","year":"1980","journal-title":"J. Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Han, S., Rajitha, K., Park, S., Lim, J., Jung, H.-Y., Kim, J., and Kim, D. (2025). Unveiling the Impact of Allulose on Oral Microbiota and Biofilm Formation via a Cariogenic Potential Assessment Platform. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1670139"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100052","DOI":"10.1016\/j.jfscie.2025.100052","article-title":"The Effect of Allulose, Sucralose, and Xylitol on Streptococcus mutans Acid Production","volume":"4","author":"Ruby","year":"2025","journal-title":"JADA Foundat. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00345-013-1091-6","article-title":"D-Mannose Powder for Prophylaxis of Recurrent Urinary Tract Infections in Women: A Randomized Clinical Trial","volume":"32","author":"Altarac","year":"2014","journal-title":"World J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1001\/jamainternmed.2024.0264","article-title":"d-Mannose for Prevention of Recurrent Urinary Tract Infection among Women: A Randomized Clinical Trial","volume":"184","author":"Hayward","year":"2024","journal-title":"JAMA Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rajasekaran, J.J., Krishnamurthy, H.K., Bosco, J., Jayaraman, V., Krishna, K., Wang, T., and Bei, K. (2024). Oral Microbiome: A Review of Its Impact on Oral and Systemic Health. Microorganisms, 12.","DOI":"10.20944\/preprints202406.1923.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.12771\/emj.2025.00101","article-title":"Relationship between Periodontitis and Systemic Health Conditions: A Narrative Review","volume":"48","author":"Kim","year":"2025","journal-title":"Ewha Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xi, M., Ruan, Q., Zhong, S., Li, J., Qi, W., Xie, C., Wang, X., Abuduxiku, N., and Ni, J. (2024). Periodontal Bacteria Influence Systemic Diseases through the Gut Microbiota. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1478362"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s40521-023-00355-4","article-title":"Does a Dysbiotic Oral Microbiome Trigger the Risk of Chronic Inflammatory Disease?","volume":"10","author":"Molina","year":"2023","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100627","DOI":"10.1016\/j.lansea.2025.100627","article-title":"Oral Health and Its Expanding Role in Systemic Disease, Cancer Outcomes, and Public Health","volume":"43","author":"Sahni","year":"2025","journal-title":"Lancet Reg. Health Southeast Asia"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Murray, P.E., Coffman, J.A., and Garcia-Godoy, F. (2024). Oral Pathogens\u2019 Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer\u2019s, Diabetes, and Other Systemic Diseases: A Public Health Crisis-A Comprehensive Review. Pathogens, 13.","DOI":"10.3390\/pathogens13121084"},{"key":"ref_26","first-page":"373","article-title":"Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds","volume":"52","author":"Hosoki","year":"2021","journal-title":"Stroke"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01049-23","DOI":"10.1128\/spectrum.01049-23","article-title":"Risk and Outcome of Infective Endocarditis in Streptococcal Bloodstream Infections according to Streptococcal Species","volume":"11","author":"Seo","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pilarczyk-Zurek, M., Sitkiewicz, I., and Koziel, J. (2022). The Clinical View on Streptococcus anginosus Group\u2014Opportunistic Pathogens Coming Out of Hiding. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.956677"},{"key":"ref_29","first-page":"25","article-title":"Role of Fusobacterium nucleatum in Periodontal Health and Disease","volume":"13","author":"Signat","year":"2011","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, Y., Shi, T., Li, Y., Huang, L., and Yin, D. (2022). Fusobacterium nucleatum: The Opportunistic Pathogen of Periodontal and Peri-Implant Diseases. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.860149"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1053\/j.gastro.2014.01.001","article-title":"Gastrointestinal Malignancy and the Microbiome","volume":"146","author":"Abreu","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhou, J., Ma, Q., Liang, J., Pan, Y., Chen, Y., Yu, S., Liu, Y., Zhang, Q., Li, Y., and Zou, J. (2025). smu_1558c-mediated regulation of growth and biofilm formation in Streptococcus mutans. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1507928"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38828","DOI":"10.1038\/srep38828","article-title":"General calibration of microbial growth in microplate readers","volume":"6","author":"Stevenson","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mira, P., Yeh, P., and Hall, B.G. (2022). Estimating microbial population data from optical density. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0276040"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gpb.2017.06.002","article-title":"Human Gut Microbiota and Gastrointestinal Cancer","volume":"16","author":"Meng","year":"2018","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s40496-024-00371-6","article-title":"Linking Periodontitis to Adverse Pregnancy Outcomes: A Comprehensive Review and Meta-analysis","volume":"11","author":"Botero","year":"2024","journal-title":"Curr. Oral Health Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/JPER.20-0104","article-title":"Porphyromonas gingivalis and Alzheimer\u2019s Disease: Recent Findings and Potential Therapies","volume":"91","author":"Ryder","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/prd.12387","article-title":"Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis","volume":"87","author":"Kuraji","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_40","first-page":"5967907","article-title":"Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals","volume":"2016","year":"2016","journal-title":"Int. J. Dent."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bordier, V., Teysseire, F., Senner, F., Schlotterbeck, G., Drewe, J., Beglinger, C., W\u00f6lnerhanssen, B.K., and Meyer-Gerspach, A.C. (2022). Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179867"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1080\/10408398.2019.1623757","article-title":"Metabolic effects of the natural sweeteners xylitol and erythritol: A comprehensive review","volume":"60","author":"Beglinger","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_43","unstructured":"U.S. Food and Drug Administration (2026, February 11). GRAS Notice (GRN) No. 893: D-Allulose (Agency Response Letter), 2019, Available online: https:\/\/www.fda.gov\/media\/138901\/download."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bloomer, R.J., Pence, J., Hellenbrand, J., Davis, A., Davis, S., Stockton, M., and Martin, K.R. (2024). Randomized Trial to Assess the Safety and Tolerability of Daily Intake of an Allulose Amino Acid-Based Hydration Beverage in Men and Women. Nutrients, 16.","DOI":"10.3390\/nu16111766"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1136\/bmj.313.7066.1180","article-title":"Xylitol Chewing Gum in Prevention of Acute Otitis Media: Double Blind Randomised Trial","volume":"313","author":"Uhari","year":"1996","journal-title":"BMJ"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/archdischild-2023-325565","article-title":"Xylitol for the prevention of acute otitis media episodes in children aged 1-5 years: A randomised controlled trial","volume":"109","author":"Persaud","year":"2024","journal-title":"Arch. Dis. Child."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1093\/eurheartj\/ehae244","article-title":"Xylitol Is Prothrombotic and Associated with Cardiovascular Risk","volume":"45","author":"Witkowski","year":"2024","journal-title":"Eur. Heart J."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/4\/884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:27:55Z","timestamp":1776241675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/4\/884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["microorganisms14040884"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14040884","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}