Effectiveness of Streptococcus salivarius probiotics on alleviating radiation-induced oral mucositis via inflammatory and microecological modulation: a prospective pragmatic interventional study in nasopharyngeal carcinoma.

2026-03-03
Frontiers in immunology 17

PubMed: 41853273
DOI: 10.3389/fimmu.2026.1745549

Study Design

Type: Clinical Trial
Population: 69 evaluable patients with nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy
Methods: Prospective, pragmatic interventional study grouped NPC patients 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 oral mucositis, with group-based trajectory modeling, univariate, multivariate, and mediation analyses.

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.

Clinical trial information

https://www.chictr.org.cn/, identifier ChiCTR2600118357.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Streptococcus salivarius	—	Delayed Oral Mucositis Onset	Beneficial	Small	View source SsM18 significantly delayed OM onset (p = 0.014)
Streptococcus salivarius	—	Reduced Oral Mucositis Severity	Beneficial	Moderate	View source 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 ... and high Beck Oral Assessment Scale (BOAS) score ... as independent predictors of 'Rapid-Onset, Severe' trajectory.