{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:17:55Z","timestamp":1777663075184,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"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. Oral Health"],"abstract":"<jats:p>\n                    Periodontal disease (PD) is an inflammatory condition affecting the supporting structures of teeth, initiated by bacterial biofilm formation.\n                    <jats:italic>Porphyromonas gulae<\/jats:italic>\n                    (\n                    <jats:italic>P. gulae<\/jats:italic>\n                    ) and\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    are key pathogens in canine and human PD, respectively, producing biofilms, volatile sulfur compounds, and proinflammatory cytokines that contribute to halitosis and tissue destruction. Cyclodextran (CI), a cyclic oligosaccharide, has previously been shown to inhibit glucan synthesis in Streptococcus mutans, but its effects on periodontal bacteria remain unexplored. This study investigated the influence of CI on\n                    <jats:italic>P. gulae<\/jats:italic>\n                    and\n                    <jats:italic>P. gingivalis in vitro<\/jats:italic>\n                    . Bacterial cultures were co-incubated with varying concentrations of a CI-dextran mix (0.313%\u20135%) for up to 24\u2005h. Biofilm formation and insoluble glucan production were assessed via fluorescence microscopy and biochemical assays. Hydrogen sulfide and methyl mercaptan levels were measured by gas chromatography, and cytokine production (IL-1\u03b2, IL-6) was quantified in murine and canine macrophage cell lines using ELISA. CI had limited bactericidal activity but significantly inhibited biofilm formation and glucan production in both bacterial species. Consequently, hydrogen sulfide and methyl mercaptan generation were markedly reduced, although CI did not directly neutralize these compounds. Furthermore, CI treatment significantly suppressed\n                    <jats:italic>P. gulae<\/jats:italic>\n                    and\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    -induced IL-1\u03b2 and IL-6 secretion in macrophages in a dose-dependent manner without cytotoxicity. These findings demonstrate that cyclodextran prevents PD-related halitosis and inflammation primarily by inhibiting biofilm formation rather than bacterial killing or direct deodorization. CI represents a promising candidate for preventive oral care in humans and companion animals, with potential to reduce the onset and progression of PD.\n                  <\/jats:p>","DOI":"10.3389\/froh.2025.1713668","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:41:30Z","timestamp":1766040090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclodextran prevents Porphyromonas gulae and Porphyromonas gingivalis induced halitosis and cytokine secretion via direct inhibition of biofilm formation"],"prefix":"10.3389","volume":"6","author":[{"given":"Megu","family":"Toyooka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao","family":"Kaneki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiharu","family":"Ohira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mio","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Fukuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0281126","DOI":"10.1371\/journal.pone.0281126","article-title":"The association between gingivitis and oral spirochetes in young cats and dogs","volume":"18","author":"Yamaki","year":"2023","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mam.2017.04.006","article-title":"Pro-Resolving mediators in the regulation of periodontal disease","volume":"58","author":"Van Dyke","year":"2017","journal-title":"Mol Aspects Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/1348-0421.12884","article-title":"Beta-Glycyrrhetinic acid inhibits the bacterial growth and biofilm formation by supragingival plaque commensals","volume":"65","author":"Dewake","year":"2021","journal-title":"Microbiol Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/jsap.12179","article-title":"Periodontal disease associated with red Complex Bacteria in dogs","volume":"55","author":"Di Bello","year":"2014","journal-title":"J Small Anim Pract"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1022838","DOI":"10.3389\/fvets.2023.1022838","article-title":"Possible association of fima genotype of Porphyromonas Gulae with the severity of periodontal disease and the number of permanent teeth in dogs","volume":"10","author":"Shirahata","year":"2023","journal-title":"Front Vet Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5360","DOI":"10.1038\/s41598-024-55842-8","article-title":"Investigation of periodontal disease development and Porphyromonas Gulae fima genotype distribution in small dogs","volume":"14","author":"Yasuda","year":"2024","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0014-5793(94)00418-8","article-title":"Purification and properties of a novel enzyme from Bacillus spp. T-3040, which catalyzes the conversion of dextran to cyclic isomaltooligosaccharides","volume":"345","author":"Oguma","year":"1994","journal-title":"FEBS Lett"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1271\/bbb.59.1861","article-title":"Inhibition of dextran and mutan synthesis by cycloisomaltooligosaccharides","volume":"59","author":"Kobayashi","year":"1995","journal-title":"Biosci Biotechnol Biochem"},{"key":"B9","doi-asserted-by":"publisher","first-page":"767","DOI":"10.3390\/vetsci12080767","article-title":"Multiwave locked system Laser treatment reduces the bacterial load in the gingival sulcus of dogs after plaque removal","volume":"12","author":"Pallante","year":"2025","journal-title":"Vet Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1515521","DOI":"10.3389\/fvets.2024.1515521","article-title":"Fusobacterium Nucleatum and Treponema Denticola are robust biomarkers for gingivitis and periodontitis in small dogs","volume":"11","author":"Kwon","year":"2024","journal-title":"Front Vet Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s10529-017-2478-z","article-title":"Decrease of insoluble glucan formation in Streptococcus Mutans by co-cultivation with Enterococcus Faecium T7 and glucanase addition","volume":"40","author":"Yu","year":"2018","journal-title":"Biotechnol Lett"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1261189","DOI":"10.3389\/fcimb.2023.1261189","article-title":"Multi-Function screening of probiotics to improve oral health and evaluating their efficacy in a rat periodontitis model","volume":"13","author":"Nie","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"107660","DOI":"10.1016\/j.micpath.2025.107660","article-title":"Lipoteichoic acid from a canine probiotic strain Lacticaseibacillus Rhamnosus possesses anti-biofilm capacity against clinically isolated canine periodontopathic Porphyromonas Species","volume":"205","author":"Park","year":"2025","journal-title":"Microb Pathog"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/1040841X.2025.2530482","article-title":"Glycosylation orchestrates virulence and pathogenicity of periodontal keystone pathogens","author":"Zhao","year":"2025","journal-title":"Crit Rev Microbiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.3390\/microorganisms13081813","article-title":"Periodontal microbial profiles across periodontal conditions in pediatric subjects. A narrative review","volume":"13","author":"Di Spirito","year":"2025","journal-title":"Microorganisms"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1589055","DOI":"10.3389\/fcimb.2025.1589055","article-title":"Effects of oral gavage with periodontal pathogens and plaque biofilm on gut Microbiota ecology and intestinal tissue architecture in mice: a mechanistic study","volume":"15","author":"Huang","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1021\/acssensors.4c02865","article-title":"Disulfide compound-impregnated paper substrate-based highly efficient colorimetric gas sensor for detection of volatile Sulfur compounds in noninvasive breath analysis","volume":"10","author":"Miura","year":"2025","journal-title":"ACS Sens"},{"key":"B18","doi-asserted-by":"publisher","first-page":"152273","DOI":"10.1016\/j.bbrc.2025.152273","article-title":"Chalcone derivatives against biofilm production of Streptococcus mutans by glucosyltransferase C inhibition","volume":"777","author":"Hatamian","year":"2025","journal-title":"Biochem Biophys Res Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0018325","DOI":"10.1128\/spectrum.00183-25","article-title":"Anti-Cariogenic activity of mutanocyclin, a secondary metabolite of Streptococcus Mutans, in mono- and multispecies biofilms","volume":"13","author":"Huang","year":"2025","journal-title":"Microbiol Spectr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5044","DOI":"10.1021\/jf2002238","article-title":"One-Pot synthesis of cycloamyloses from sucrose by dual enzyme treatment: combined reaction of amylosucrase and 4-alpha-glucanotransferase","volume":"59","author":"Kim","year":"2011","journal-title":"J Agric Food Chem"},{"key":"B21","doi-asserted-by":"publisher","first-page":"110023","DOI":"10.1016\/j.enzmictec.2022.110023","article-title":"Carbohydrate-Binding module of cycloisomaltooligosaccharide glucanotransferase from Thermoanaerobacter Thermocopriae improves its cyclodextran production","volume":"157","author":"Hong","year":"2022","journal-title":"Enzyme Microb Technol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.4014\/jmb.1910.10022","article-title":"Carboxy-terminal region of a thermostable citase from Thermoanaerobacter Thermocopriae has the ability to produce long isomaltooligosaccharides","volume":"29","author":"Jeong","year":"2019","journal-title":"J Microbiol Biotechnol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"7781","DOI":"10.3390\/ijms26167781","article-title":"Porphyromonas Gingivalis groel accelerates abdominal aortic aneurysm formation by induction of M1 polarization in macrophages","volume":"26","author":"Lin","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.3390\/microorganisms13071701","article-title":"Impact of live ligilactobacillus Salivarius Ccfm1332 and its postbiotics on Porphyromonas Gingivalis colonization, alveolar bone resorption and inflammation in a rat model of periodontitis","volume":"13","author":"Hong","year":"2025","journal-title":"Microorganisms"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1007\/s00204-023-03593-2","article-title":"Effects of low concentrations of ozone gas exposure on percutaneous oxygen saturation and inflammatory responses in a mouse model of Dermatophagoides Farinae-induced asthma","volume":"97","author":"Ohira","year":"2023","journal-title":"Arch Toxicol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jphs.2025.02.001","article-title":"Intraoral treatment of Persimmon Tannin, a polyphenol extracted from persimmon, significantly ameliorates gingivitis, plaque and halitosis via directly influence the periodontal Bacteria Porphyromonasgulae","volume":"157","author":"Toyooka","year":"2025","journal-title":"J Pharmacol Sci"}],"container-title":["Frontiers in Oral Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2025.1713668\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:41:31Z","timestamp":1766040091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2025.1713668\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":26,"alternative-id":["10.3389\/froh.2025.1713668"],"URL":"https:\/\/doi.org\/10.3389\/froh.2025.1713668","relation":{},"ISSN":["2673-4842"],"issn-type":[{"value":"2673-4842","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"1713668"}}