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

## TL;DR

This study shows that a specific probiotic, SsM18, can reduce the severity and duration of radiation-induced mouth sores in cancer patients.

## Contribution

The study demonstrates that SsM18 is more effective than SsK12 in improving outcomes for radiation-induced oral mucositis.

## Key findings

- SsM18 delayed the onset and reduced the duration of severe oral mucositis compared to no probiotic.
- Elevated IL-6 levels and high BOAS scores predicted a more severe OM trajectory.
- The Teeth subdomain of BOAS was linked to earlier OM onset, partially mediated by IL-6.

## Abstract

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.

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.

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%).

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.

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