ORIGINAL RESEARCH article
Front. Immunol.
Sec. Mucosal Immunity
Effectiveness of Streptococcus salivarius probiotics on Alleviating Radiation-Induced Oral Mucositis via Inflammatory and Microecological Modulation: A Prospective Pragmatic Interventional Study in Nasopharyngeal Carcinoma
Xiaotong Huang 1,2
Hui Feng 1
Ye Tan 1
Quan Wang 3
Jie-Mei Wei 4
Zhao-Dong Huang 4
Haijun Lu 1
Xin-Tong Wang 1
1. The Affiliated Hospital of Qingdao University, Qingdao, China
2. Qingdao University, Qingdao, China
3. Qingdao Central Hospital of University of Health and Rehabilitation Sciences, Qingdao, China
4. Linyi Central Hospital, Linyi, China
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Abstract
Background: 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. Methods: This prospective, pragmatic interventional study grouped nasopharyngeal carcinoma (NPC) patients receiving chemoradiotherapy by probiotic exposure: no probiotic, Streptococcus salivarius K12 (SsK12), or Streptococcus salivarius 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. Results: 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 (p = 0.014), reduced SOM duration (p = 0.019), and shortened total OM duration (p = 0.031), outperforming SsK12. GBTM identified two distinct OM trajectories: 'Rapid-Onset, Severe' group and 'Late-Onset, Mild' group. Multivariate analysis revealed that elevated log-transformed Interleukin-6 levels (odds ratio [OR] = 4.20, p = 0.020), and high Beck Oral Assessment Scale (BOAS) score (OR=3.06, p = 0.044) as independent predictors of 'Rapid-Onset, Severe' trajectory. The Teeth subdomain of BOAS was identified as an independent predictor for earlier OM onset (p = 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: 30–50%). Conclusions: 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.
Summary
Keywords
ecological inflammation, IL-6, IL-8, oral microbiome, Probiotics, Radiation-Induced Oral Mucositis, Streptococcus salivarius K12, Streptococcus salivarius M18
Received
13 November 2025
Accepted
13 February 2026
Copyright
© 2026 Huang, Feng, Tan, Wang, Wei, Huang, Lu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiaotong Huang; Haijun Lu; Xin-Tong Wang
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