{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:45:41Z","timestamp":1789595141076,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Orthodontics, School of Dental Medicine, Tsurumi University"},{"name":"2024 Academic Research Grant from the Society for Tsurumi University School of Dental Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Halitosis is frequently observed in patients undergoing orthodontic treatment with multibracket appliances, primarily due to volatile sulfur compounds (VSCs) produced by oral anaerobic bacteria. Cetylpyridinium chloride (CPC) is a widely used antimicrobial agent in oral care products and may help alleviate halitosis.This study aimed to evaluate the effects of 0.05% CPC mouthwash on halitosis, oral hygiene indices, and the tongue microbiota in orthodontic patients with elevated VSC levels. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 30 orthodontic patients with elevated VSCs (\u2265150 ppb) were assigned to a CPC mouthwash group or a placebo group. Participants used the assigned mouthwash three times daily for 1 month. Halitosis was quantitatively assessed by gas chromatography (Oral Chroma\u2122), and oral hygiene parameters including Plaque Index (PI), Gingival Index (GI), Tongue Coating Index (TCI), and unstimulated salivary flow rate were evaluated at baseline and after the intervention. The tongue microbiota was analyzed by 16S rRNA sequencing. Results: The CPC mouthwash group showed significant reductions in total VSCs, hydrogen sulfide, methyl mercaptan, PI, GI, and TCI (p &lt; 0.05), while salivary flow rate and dimethyl sulfide remained unchanged. Microbiome analysis revealed decreases in halitosis-associated genera (Actinomyces, Corynebacterium, Tannerella) and increases in beneficial species such as Streptococcus salivarius. Conclusions: CPC mouthwash (0.05%) effectively reduced halitosis and improved oral hygiene parameters in orthodontic patients, likely through modulation of the tongue microbiota. This mouthwash may serve as a safe and practical adjunct to conventional oral hygiene practices during orthodontic treatment.<\/jats:p>","DOI":"10.3390\/jcm14134576","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"4576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of 0.05% Cetylpyridinium Chloride Mouthwash on Halitosis and Tongue Microbiota in Patients Undergoing Orthodontic Treatment: A Double-Blind Randomized Clinical Trial"],"prefix":"10.3390","volume":"14","author":[{"given":"Natsuki","family":"Shiina","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Shimpo","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kou","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiko","family":"Sekiya","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tomonari","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1902\/jop.1977.48.1.13","article-title":"Production and origin of oral malodor: A review of mechanisms and methods of analysis","volume":"48","author":"Tonzetich","year":"1977","journal-title":"J. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jdent.2007.04.009","article-title":"A review of the current literature on aetiology and measurement methods of halitosis","volume":"35","author":"Feenstra","year":"2007","journal-title":"J. Dent."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/jcpe.12090","article-title":"Efficacy of different mouthrinse formulations in reducing oral malodour: A randomized clinical trial","volume":"40","author":"Dadamio","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1399-302X.1990.tb00645.x","article-title":"The formation of hydrogen sulfide and methyl mercaptan by oral bacteria","volume":"5","author":"Persson","year":"1990","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1902\/jop.1992.63.9.776","article-title":"Measurement of oral malodor: Current methods and future prospects","volume":"63","author":"Rosenberg","year":"1992","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ajodo.2009.03.055","article-title":"Effect of fixed appliances on oral malodor","volume":"139","author":"Babacan","year":"2011","journal-title":"Am. J. Orthod. Dentofacial Orthop."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Santonocito, S., and Polizzi, A. (2022). Oral Microbiota Changes during Orthodontic Treatment. Front. Biosci. (Elite Ed.), 14.","DOI":"10.31083\/j.fbe1403019"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"S\u00f6k\u00fcc\u00fc, O., Akp\u0131nar, A., \u00d6zdemir, H., Birlik, M., and \u00c7al\u0131\u015f\u0131r, M. (2016). The effect of fixed appliances on oral malodor from beginning of treatment till 1 year. BMC Oral Health, 16.","DOI":"10.1186\/s12903-016-0174-3"},{"key":"ref_9","first-page":"1064","article-title":"The influence of fixed orthodontic appliances on halitosis","volume":"123","author":"Zurfluh","year":"2013","journal-title":"Schweiz Monatsschr Zahnmed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s00056-010-1040-6","article-title":"Halitosis, oral health and quality of life during treatment with Invisalign(\u00ae) and the effect of a low-dose chlorhexidine solution","volume":"71","author":"Schaefer","year":"2010","journal-title":"J. Orofac. Orthop."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5005\/jcdp-6-1-1","article-title":"Antibacterial and antiplaque effects of a novel, alcohol-free oral rinse with cetylpyridinium chloride","volume":"6","author":"Witt","year":"2005","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_12","first-page":"15A","article-title":"Comparative clinical trial of two antigingivitis mouthrinses","volume":"18","author":"Witt","year":"2005","journal-title":"Am. J. Dent."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-051X.2007.01187.x","article-title":"Efficacy of two alcohol-free cetylpyridinium chloride mouthwashes: A randomized double-blind crossover study","volume":"35","author":"Rawlinson","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1177\/00220345970760110801","article-title":"Isolation of Enterobacteriaceae from the mouth and potential association with malodor","volume":"76","author":"Goldberg","year":"1997","journal-title":"J. Dent. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/jcpe.13127","article-title":"Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review and network meta-analyses","volume":"46","author":"Figuero","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/idh.12413","article-title":"Clinical efficacy of a new cetylpyridinium chloride-hyaluronic acid-based mouthrinse compared to chlorhexidine and placebo mouthrinses: A 21-day randomized clinical trial","volume":"18","author":"Tadakamadla","year":"2020","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_17","first-page":"e47","article-title":"Efficacy of two mouthwashes with cetylpyridinium chloride: A controlled randomized clinical trial","volume":"31","author":"Cavagni","year":"2017","journal-title":"Braz. Oral Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1601-5037.2008.00344.x","article-title":"The effect of cetylpyridinium chloride-containing mouth rinses as adjuncts to toothbrushing on plaque and parameters of gingival inflammation: A systematic review","volume":"6","author":"Haps","year":"2008","journal-title":"Int J Dent Hyg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Musa, H., Pa\u0219ca, I.G., Popa, M., B\u0103lean, O., Dumitrescu, R., Ro\u0219ianu, R.S., G\u0103lu\u0219can, A., and Oancea, R. (2025). Halitosis and Quality of Life in Young Orthodontic Patients: A Cross-Sectional Assessment of Mouthwash Use and Traditional, Rotative, and Sonic Toothbrushes. Medicina, 61.","DOI":"10.3390\/medicina61050815"},{"key":"ref_20","first-page":"456","article-title":"Effect of an essential oil-containing mouth rinse on VSC-producing bacteria on the tongue","volume":"42","author":"Thaweboon","year":"2011","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/idh.12572","article-title":"Self-perceived halitosis among young adults undergoing orthodontic treatment","volume":"20","author":"Banjar","year":"2022","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/idh.12046","article-title":"Relationship between halitosis and periodontal disease-associated oral bacteria in tongue coatings","volume":"12","author":"Amou","year":"2014","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.oooo.2020.09.006","article-title":"Novel oral biomarkers predicting oral malodor","volume":"130","author":"Takaesu","year":"2020","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1177\/00220345241230067","article-title":"Tongue-Coating Microbial and Metabolic Characteristics in Halitosis","volume":"103","author":"Zhang","year":"2024","journal-title":"J. Dent. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/00016357.2020.1754459","article-title":"Characterization of oral bacteria in the tongue coating of patients with halitosis using 16S rRNA analysis","volume":"78","author":"Oshiro","year":"2020","journal-title":"Acta Odontol. Scand."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gomar-Vercher, S., Sim\u00f3n-Soro, \u00c1., Montiel-Company, J.M., Almerich-Silla, J.M., and Mira, A. (2018). Stimulated and unstimulated saliva samples have significantly different bacterial profiles. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198021"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jdent.2014.12.010","article-title":"Assessment of the effectiveness of mouthwashes in reducing cariogenic biofilm in orthodontic patients: A systematic review","volume":"43","author":"Pithon","year":"2015","journal-title":"J. Dent."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"036010","DOI":"10.1088\/1752-7163\/aa7c24","article-title":"The tongue microbiome in healthy subjects and patients with intra-oral halitosis","volume":"11","author":"Seerangaiyan","year":"2017","journal-title":"J. Breath Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.otohns.2005.09.036","article-title":"The relationship between oral malodor and volatile sulfur compound-producing bacteria","volume":"135","author":"Krespi","year":"2006","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/omi.12259","article-title":"Induction and inhibition of oral malodor","volume":"34","author":"Suzuki","year":"2019","journal-title":"Mol. Oral Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1128\/AEM.02304-09","article-title":"Relationship between oral malodor and the global composition of indigenous bacterial populations in saliva","volume":"76","author":"Takeshita","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1902\/jop.2003.74.1.32","article-title":"The relationship between volatile sulfur compounds and major halitosis-inducing factors","volume":"74","author":"Lee","year":"2003","journal-title":"J. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"034001","DOI":"10.1088\/1752-7163\/aaa3a1","article-title":"Tongue coating: Its characteristics and role in intra-oral halitosis and general health\u2014A review","volume":"12","author":"Seerangaiyan","year":"2018","journal-title":"J. Breath Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/JCM.41.2.558-563.2003","article-title":"Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients","volume":"41","author":"Kazor","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mao, X., Hiergeist, A., Auer, D.L., Scholz, K.J., Muehler, D., Hiller, K.-A., Maisch, T., Buchalla, W., Hellwig, E., and Gessner, A. (2022). Ecological effects of daily antiseptic treatment on microbial composition of saliva-grown microcosm biofilms and selection of resistant phenotypes. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.934525"},{"key":"ref_36","first-page":"e384","article-title":"Assessing the association between unstimulated whole salivary flow rate (UWSFR) and oral health status among healthy adult subjects: A cross-sectional study","volume":"23","author":"Idrees","year":"2018","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"c332","DOI":"10.1136\/bmj.c332","article-title":"CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials","volume":"340","author":"Schulz","year":"2010","journal-title":"BMJ"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/ejo\/cjad036","article-title":"The effect of mastic mouthwash on halitosis and oral hygiene in orthodontic patients: A randomized clinical trial","volume":"45","author":"Tsironi","year":"2023","journal-title":"Eur. J. Orthod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/00016356408993968","article-title":"Periodontal Disease in Pregnancy II. Correlation between Oral Hygiene and Periodontal Condition","volume":"22","author":"Silness","year":"1964","journal-title":"Acta Odontol. Scand."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.archger.2007.08.005","article-title":"Tongue-coating as risk indicator for aspiration pneumonia in edentate elderly","volume":"47","author":"Abe","year":"2008","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Choi, H.-N., Cho, Y.-S., and Koo, J.-W. (2021). The effect of mechanical tongue cleaning on oral malodor and tongue coating. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19010108"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"K\u0131ranatl\u0131, M., Yurtta\u015f, M., G\u00fcng\u00f6r, M., and Canbaz Kabay, S. (2024). Evaluation of major salivary glands with ultrasonography in multiple sclerosis patients. BMC Oral Health, 24.","DOI":"10.1186\/s12903-024-04007-0"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/ejo\/cjx096","article-title":"Clinical and microbiological effects of the use of a cetylpyridinium chloride dentifrice and mouth rinse in orthodontic patients: A 3-month randomized clinical trial","volume":"40","author":"Herrera","year":"2018","journal-title":"Eur. J. Orthod."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4576\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:16Z","timestamp":1760032816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":43,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134576"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134576","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}