{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:23:40Z","timestamp":1788780220831,"version":"build-2803163510"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiation-induced oral mucositis (OM) is a prevalent and debilitating complication of head and neck radiotherapy, yet its severity varies markedly between patients. Emerging evidence suggests that this heterogeneity is influenced by the pre-existing oral microbiome and host inflammatory tone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective, pragmatic interventional study grouped nasopharyngeal carcinoma (NPC) patients receiving chemoradiotherapy by probiotic exposure: no probiotic,\n                      <jats:italic>Streptococcus salivarius<\/jats:italic>\n                      K12 (SsK12), or\n                      <jats:italic>Streptococcus salivarius<\/jats:italic>\n                      M18 (SsM18). Weekly oral assessments were used to characterize the onset, duration, and severity of OM. Group-based trajectory modeling (GBTM) was used to identify OM trajectories. Univariate, multivariate, and mediation analyses were used to explore associated factors and potential relationships.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 69 evaluable patients, OM occurred in 95.7%, with severe OM (SOM) in 42.4%. Compared with non-probiotic group, SsM18 significantly delayed OM onset (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.014), reduced SOM duration (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.019), and shortened total OM duration (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.031), outperforming SsK12. GBTM identified two distinct OM trajectories: \u2018Rapid-Onset, Severe\u2019 group and \u2018Late-Onset, Mild\u2019 group. Multivariate analysis revealed that elevated log-transformed Interleukin-6 levels (odds ratio [OR] = 4.20,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.020), and high Beck Oral Assessment Scale (BOAS) score (OR = 3.06,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.044) as independent predictors of \u2018Rapid-Onset, Severe\u2019 trajectory. The Teeth subdomain of BOAS was identified as an independent predictor for earlier OM onset (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.042). Mediation analysis suggested that the association between a higher Teeth subdomain score and OM was partially mediated by IL-6 elevation (proportion mediated: 30\u201350%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Radiotherapy-induced OM was associated with baseline oral health and inflammatory status. SsM18 supplementation was associated with improved OM-related outcomes, suggesting a potential role for precision probiotic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial information<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/<\/jats:ext-link>\n                      , identifier ChiCTR2600118357.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1745549","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:58:44Z","timestamp":1772524724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness of Streptococcus salivarius probiotics on alleviating radiation-induced oral mucositis via inflammatory and microecological modulation: a prospective pragmatic interventional study in nasopharyngeal carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao-Tong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]},{"name":"Medical College, Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Qingdao Central Hospital of Rehabilitation University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Mei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Linyi Central Hospital","place":["Linyi, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Dong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Invasive Technology, Linyi Central Hospital","place":["Linyi, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ctrv.2017.07.003","article-title":"Treatment of late sequelae after radiotherapy for head and neck cancer","volume":"59","author":"Strojan","year":"2017","journal-title":"Cancer Treat Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e2337265","DOI":"10.1001\/jamanetworkopen.2023.37265","article-title":"Severe oral mucositis after intensity-modulated radiation therapy for head and neck cancer","volume":"6","author":"Iovoli","year":"2023","journal-title":"JAMA Netw Open"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-024-03706-y","article-title":"The prevalence of oral mucositis after radiotherapy in patients with Head and Neck Cancer and its associated factors: a meta-analysis","volume":"27","author":"Li","year":"2025","journal-title":"Clin Transl Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.01507","article-title":"Phase IIb, randomized, double-blind trial of GC4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer","volume":"37","author":"Anderson","year":"2019","journal-title":"J Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.32.4103","article-title":"Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial","volume":"29","author":"Henke","year":"2011","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.32.4095","article-title":"Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study","volume":"29","author":"Le","year":"2011","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-015-3694\u20136","article-title":"Radiation induced oral mucositis: a review of current literature on prevention and management","volume":"273","author":"Mallick","year":"2016","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.08.006","article-title":"Mucositis: The impact, biology and therapeutic opportunities of oral mucositis","volume":"45","author":"Sonis","year":"2009","journal-title":"Oral Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00089","article-title":"Radiation-induced oral mucositis","volume":"7","author":"Maria","year":"2017","journal-title":"Front Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3322\/canjclin.51.5.290","article-title":"Oral mucositis complicating chemotherapy and\/or radiotherapy: options for prevention and treatment","volume":"51","author":"K\u00f6stler","year":"2001","journal-title":"CA Cancer J Clin"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04169","article-title":"Chemotherapy-induced and\/or radiation therapy-induced oral mucositis\u2013complicating the treatment of cancer","volume":"6","author":"Naidu","year":"2004","journal-title":"Neoplasia"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1002\/j.0022-0337.2005.69.8.tb03989.x","article-title":"Cancer therapy-related oral mucositis","volume":"69","author":"Redding","year":"2005","journal-title":"J Dent Educ"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007\u20130197","article-title":"Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing","volume":"25","author":"Chamberlain","year":"2007","journal-title":"Stem Cells"},{"key":"B14","first-page":"3","article-title":"Pathobiology of oral mucositis: novel insights and opportunities","volume":"5","author":"Sonis","year":"2007","journal-title":"J Support Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/s1368-8375(97)00053-5","article-title":"Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity","volume":"34","author":"Sonis","year":"1998","journal-title":"Oral Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/hed.10326","article-title":"Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: diagnosis and management of mucositis","volume":"26","author":"Scully","year":"2004","journal-title":"Head Neck"},{"key":"B17","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.radonc.2018.04.023","article-title":"Distinct shifts in the oral microbiota are associated with the progression and aggravation of mucositis during radiotherapy","volume":"129","author":"Hou","year":"2018","journal-title":"Radiother Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ebiom.2017.02.002","article-title":"The potential effect of oral microbiota in the prediction of mucositis during radiotherapy for nasopharyngeal carcinoma","volume":"18","author":"Zhu","year":"2017","journal-title":"EBioMedicine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12398","article-title":"Oral health's inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions","volume":"87","author":"Kapila","year":"2021","journal-title":"Periodontol 2000"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31907","article-title":"A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma","volume":"125","author":"Jiang","year":"2019","journal-title":"Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26619","article-title":"Chemoradiation therapy changes oral microbiome and metabolomic profiles in patients with oral cavity cancer and oropharyngeal cancer","volume":"43","author":"Lim","year":"2021","journal-title":"Head Neck"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33161","article-title":"Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck","volume":"126","author":"Reyes-Gibby","year":"2020","journal-title":"Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"13201","DOI":"10.1038\/s41598-020-70024-y","article-title":"Randomised, double-blind, placebo-controlled trial of oral probiotic Streptococcus salivarius M18 on head and neck cancer patients post-radiotherapy: a pilot study","volume":"10","author":"Vesty","year":"2020","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1070322","article-title":"Distinctive microbiota of delayed healing of oral mucositis after radiotherapy of nasopharyngeal carcinoma","volume":"12","author":"Jiang","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.06.010","article-title":"Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced mucositis in patients with head and neck cancer: a randomized double-blind placebo-controlled study","volume":"48","author":"Sharma","year":"2012","journal-title":"Eur J Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2024.106785","article-title":"Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: A systematic review and meta-analysis","volume":"193","author":"Lin","year":"2024","journal-title":"Microb Pathog"},{"key":"B27","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1186\/s12903-025-05876\u20139","article-title":"Efficacy and tolerability of probiotics, prebiotics, and symbiotics consumption on oral complications of patients with thyroid and head and neck cancers: a systematic review and meta-analysis","volume":"25","author":"Shafiei","year":"2025","journal-title":"BMC Oral Health"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-022-10010\u20130","article-title":"Interferon gamma response in human saliva following exposure to the oral probiotic streptococcus salivarius BLIS K12","volume":"16","author":"Laws","year":"2024","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-021-09822\u20133","article-title":"Human systemic immune response to ingestion of the oral probiotic streptococcus salivarius BLIS K12","volume":"13","author":"Laws","year":"2021","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-023-10116-z","article-title":"The role of biotics as a therapeutic strategy for oral mucositis - A systematic review","volume":"16","author":"Frey-Furtado","year":"2024","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1200\/jco.23.00837","article-title":"Streptococcus salivarius K12 alleviates oral mucositis in patients undergoing radiotherapy for Malignant head and neck tumors: A randomized controlled trial","volume":"42","author":"Peng","year":"2024","journal-title":"J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-018-9398-7","article-title":"Assessment of efficacy of BLIS-producing probiotic K12 for the prevention of group A streptococcus pharyngitis: a short communication","volume":"11","author":"Di Pierro","year":"2019","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3390\/ijerph18041629","article-title":"Investigation of changes in saliva in radiotherapy-induced head neck cancer patients","volume":"18","author":"Winter","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2024.110279","article-title":"Radiation-associated changes in saliva composition of head and neck cancer patients: A systematic review","volume":"196","author":"Staruch","year":"2024","journal-title":"Radiother Oncol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3882","DOI":"10.3390\/nu15183882","article-title":"Antigingivitis and antiplaque effects of oral probiotic containing the streptococcus salivarius M18 strain: A randomized clinical trial","volume":"15","author":"Babina","year":"2023","journal-title":"Nutrients"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.113","article-title":"Developing oral probiotics from Streptococcus salivarius","volume":"7","author":"Wescombe","year":"2012","journal-title":"Future Microbiol"},{"key":"B37","volume-title":"Generally recognized as safe (GRAS) notice no. 807 for streptococcus salivarius M18","year":"2018"},{"key":"B38","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.radonc.2017.10.032","article-title":"International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma","volume":"126","author":"Lee","year":"2018","journal-title":"Radiother Oncol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.radonc.2015.07.041","article-title":"CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines","volume":"117","author":"Brouwer","year":"2015","journal-title":"Radiother Oncol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.radonc.2017.10.016","article-title":"Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines","volume":"126","author":"Gr\u00e9goire","year":"2018","journal-title":"Radiother Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-011-0015-x","article-title":"The ICRU Report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT)","volume":"188","author":"Hodapp","year":"2012","journal-title":"Strahlenther Onkol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4037\/ajcc2011359","article-title":"Effects of systematic oral care in critically ill patients: a multicenter study","volume":"20","author":"Ames","year":"2011","journal-title":"Am J Crit Care"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/nicc.12570","article-title":"British Association of Critical Care Nurses: Evidence-based consensus paper for oral care within adult critical care units","volume":"26","author":"Collins","year":"2021","journal-title":"Nurs Crit Care"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/00002820-197906000-00002","article-title":"Impact of a systematic oral care protocol on stomatitis after chemotherapy","volume":"2","author":"Beck","year":"1979","journal-title":"Cancer Nurs"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2006.10.009","article-title":"Test for additive interaction in proportional hazards models","volume":"17","author":"Li","year":"2007","journal-title":"Ann Epidemiol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/s0261-5614(02)00214-5","article-title":"Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials","volume":"22","author":"Kondrup","year":"2003","journal-title":"Clin Nutr"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3747\/co.26.4819","article-title":"Human papillomavirus-associated oropharyngeal cancer: review of current evidence and management","volume":"26","author":"You","year":"2019","journal-title":"Curr Oncol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3109\/00016489.2014.927590","article-title":"The impact of HPV infection, smoking history, age and operability of the patient on disease-specific survival in a geographically defined cohort of patients with oropharyngeal squamous cell carcinoma","volume":"134","author":"Lj\u00f8kjel","year":"2014","journal-title":"Acta Otolaryngol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1186\/s12885-015-1902\u20139","article-title":"Smoking and nasopharyngeal carcinoma mortality: a cohort study of 101,823 adults in Guangzhou, China","volume":"15","author":"Lin","year":"2015","journal-title":"BMC Cancer"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e016582","DOI":"10.1136\/bmjopen-2017\u2013016582","article-title":"Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies","volume":"7","author":"Long","year":"2017","journal-title":"BMJ Open"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.042","article-title":"Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA alcoholic hepatitis consortia","volume":"150","author":"Crabb","year":"2016","journal-title":"Gastroenterology"},{"key":"B52","first-page":"5","article-title":"Ratio of neutrophil to lymphocyte counts\u2013rapid and simple parameter of systemic inflammation and stress in critically ill","volume":"102","author":"Zahorec","year":"2001","journal-title":"Bratisl Lek Listy"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-14\u20130442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"8002","DOI":"10.3390\/ijms22158002","article-title":"Inflammation-related biomarkers for the prediction of prognosis in colorectal cancer patients","volume":"22","author":"Yamamoto","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16865","article-title":"Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(80)90246-9","article-title":"Prognostic nutritional index in gastrointestinal surgery","volume":"139","author":"Buzby","year":"1980","journal-title":"Am J Surg"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2021.01.007","article-title":"The role of sugar-rich diet and salivary proteins in dental plaque formation and oral health","volume":"63","author":"Gasmi Benahmed","year":"2021","journal-title":"J Oral Biosci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s007840050106","article-title":"Acid formation in sucrose-exposed dental plaque in relation to caries incidence in schoolchildren","volume":"4","author":"Borgstr\u00f6m","year":"2000","journal-title":"Clin Oral Investig"},{"key":"B59","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1007\/bf01569826","article-title":"Oxygen metabolism, oxidative stress and acid-base physiology of dental plaque biofilms","volume":"15","author":"Marquis","year":"1995","journal-title":"J Ind Microbiol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0300-5712(83)90184-7","article-title":"The role of sugar in the aetiology of dental caries. 3. The physiochemical evidence","volume":"11","author":"Edgar","year":"1983","journal-title":"J Dent"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The biology of streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiol Spectr"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1235936","article-title":"Cellular RNA and DNA sensing pathways are essential for the dose-dependent response of human monocytes to ionizing radiation","volume":"14","author":"Mikhalkevich","year":"2023","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717x-5\u201316","article-title":"Cytokines levels, severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer\u2013a prospective pilot study","volume":"5","author":"Meirovitz","year":"2010","journal-title":"Radiat Oncol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27313","article-title":"Correlations between the severity of radiation-induced oral mucositis and salivary epidermal growth factor as well as inflammatory cytokines in patients with head and neck cancer","volume":"45","author":"Xu","year":"2023","journal-title":"Head Neck"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1994.tb00030.x","article-title":"Effect of chronic alcohol consumption on the morphology of the oral mucosa","volume":"18","author":"Maier","year":"1994","journal-title":"Alcohol Clin Exp Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.294.3696","article-title":"Effects of alcohol on the morphological and structural changes in oral mucosa","volume":"29","author":"Feng","year":"2013","journal-title":"Pak J Med Sci"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2016.01.010","article-title":"Mucositis in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus statements","volume":"100","author":"De Sanctis","year":"2016","journal-title":"Crit Rev Oncol Hematol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"5705","DOI":"10.3390\/cancers15235705","article-title":"Predictive factors for chemoradiation-induced oral mucositis and dysphagia in head and neck cancer: A scoping review","volume":"15","author":"Nicol","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1128\/iai.68.9.5284-5292.2000","article-title":"Cytokine responses to treponema pectinovorum and treponema denticola in human gingival fibroblasts","volume":"68","author":"Nixon","year":"2000","journal-title":"Infect Immun"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00109\u201310","article-title":"Oral bacteria as potential probiotics for the pharyngeal mucosa","volume":"76","author":"Guglielmetti","year":"2010","journal-title":"Appl Environ Microbiol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1180642","article-title":"Towards unravelling biological mechanisms behind radiation-induced oral mucositis via mass spectrometry-based proteomics","volume":"13","author":"Subedi","year":"2023","journal-title":"Front Oncol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2013.758711","article-title":"Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and\/or tonsillitis caused by Streptococcus pyogenes in adults","volume":"13","author":"Di Pierro","year":"2013","journal-title":"Expert Opin Biol Ther"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00188\u201308","article-title":"The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis","volume":"76","author":"Cosseau","year":"2008","journal-title":"Infect Immun"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0569\u20134","article-title":"Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12","volume":"27","author":"Power","year":"2008","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00334.x","article-title":"Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction","volume":"22","author":"Horz","year":"2007","journal-title":"Oral Microbiol Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.23736\/s0026-4946.18.05182\u20134","article-title":"Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo-tonsillitis and acute otitis media in children: a retrospective analysis in not-recurrent pediatric subjects","volume":"70","author":"Di Pierro","year":"2018","journal-title":"Minerva Pediatr"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S38859","article-title":"Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and\/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media","volume":"5","author":"Di Pierro","year":"2012","journal-title":"Int J Gen Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.2147\/ccide.S93066","article-title":"Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study","volume":"7","author":"Di Pierro","year":"2015","journal-title":"Clin Cosmet Investig Dent"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.09.61","article-title":"Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics","volume":"4","author":"Wescombe","year":"2009","journal-title":"Future Microbiol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2147\/tcrm.S96134","article-title":"Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study","volume":"12","author":"Gregori","year":"2016","journal-title":"Ther Clin Risk Manag"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02265\u201306","article-title":"Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12","volume":"73","author":"Hyink","year":"2007","journal-title":"Appl Environ Microbiol"},{"key":"B82","article-title":"Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius","volume":"119","author":"Tagg","year":"2004","journal-title":"Indian J Med Res"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.056663\u20130","article-title":"Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial","volume":"62","author":"Burton","year":"2013","journal-title":"J Med Microbiol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1177\/22808000251376427","article-title":"Probiotics for caries prevention: A narrative review","volume":"23","author":"Nizami","year":"2025","journal-title":"J Appl Biomater Funct Mater"},{"key":"B85","doi-asserted-by":"publisher","first-page":"e65991","DOI":"10.1371\/journal.pone.0065991","article-title":"Persistence of the oral probiotic Streptococcus salivarius M18 is dose dependent and megaplasmid transfer can augment their bacteriocin production and adhesion characteristics","volume":"8","author":"Burton","year":"2013","journal-title":"PLoS One"},{"key":"B86","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3390\/biom14050560","article-title":"Systemic anti-inflammatory agents in the prevention of chemoradiation-induced mucositis: A review of randomised controlled trials","volume":"14","author":"Mohammed","year":"2024","journal-title":"Biomolecules"},{"key":"B87","doi-asserted-by":"publisher","first-page":"12283","DOI":"10.1038\/s41598-021-91600-w","article-title":"Oral pH value predicts the incidence of radiotherapy related caries in nasopharyngeal carcinoma patients","volume":"11","author":"Li","year":"2021","journal-title":"Sci Rep"},{"key":"B88","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12903-021-01606-z","article-title":"Streptococcus salivarius inhibits immune activation by periodontal disease pathogens","volume":"21","author":"MacDonald","year":"2021","journal-title":"BMC Oral Health"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1745549\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:58:47Z","timestamp":1772524727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1745549\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":88,"alternative-id":["10.3389\/fimmu.2026.1745549"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1745549","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"article-number":"1745549"}}