Abstract

BackgroundOral mucositis is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy, leading to poor quality of life. Limitations of the current interventions on radiation-induced oral mucositis (RIOM) urge the development of novel therapeutics. Here, we evaluated the treatment outcome of probiotic Streptococcus salivarius K12 on RIOM mice, and oral microbiota that is associated with the progress of RIOM was further investigated.MethodsAn experimental RIOM mouse model was established, and S. salivarius K12 was applied to the mouse oral cavity daily. Histological analyses were performed to evaluate the severity of oral mucositis and the treatment outcome of S. salivarius K12. The oral microbiota of mice was further analyzed by 16S rRNA sequencing, microbial culture and qPCR.Results Irradiation induced conspicuous mucositis in the oral cavity of mice. S. salivarius K12 treatment was beneficial for the healing of RIOM, as reflected by reduced ulcer size, increased basal layer epithelial cellularity and mucosal thickness, and elevated epithelial proliferation and attenuated apoptosis. RIOM mice presented significant oral microbial dysbiosis, with an overgrowth of oral anaerobes. S. salivarius K12 treatment reconstituted the oral microbiota and decreased the abundance of oral anaerobes of RIOM mice. In addition, S. salivarius K12 treatment inhibited NI1060 in Pasteurella genus and downregulated the expression of nitrate reductase.Conclusions S. salivarius K12 treatment can alleviate RIOM and reconstituted the dysbiotic oral microbiota in mice. S. salivarius K12 may represent a promising adjuvant treatment to improve the quality of life of cancer patients receiving radiotherapy.

Highlights

  • Oral mucositis, characterized by inflammation and mucosal damage of oral mucosa, is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy

  • Topical application of S. salivarius K12 significantly reduced the severity of oral mucositis in irradiated mice (Figure 1C–E)

  • hematoxylin and eosin (H&E) staining showed conspicuous mucosal hypoplasia and ulceration in the tongue of irradiated mice, while S. salivarius K12 treatment partially restored the integrity of the lingual mucosa (Figure 2A)

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Summary

Introduction

Oral mucositis, characterized by inflammation and mucosal damage of oral mucosa, is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy. The incidence of oral mucositis is almost 100% in head and neck cancer patients receiving radiotherapy [1, 2]. 85% of patients receiving intensive chemotherapy for hematopoietic stem cell transplant develop oral mucositis [3]. Oral mucositis induced by radiotherapy/chemotherapy can cause pain, dysphagia and malnutrition, seriously affecting the quality of life of patients and interrupting anti-cancer treatment. There is still a need for the development of novel therapeutics for the better management of oral mucositis. Oral mucositis is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy, leading to poor quality of life. Limitations of the current interventions on radiation-induced oral mucositis (RIOM) urge the development of novel therapeutics. We evaluated the treatment outcome of probiotic Streptococcus salivarius K12 on RIOM mice, and oral microbiota that is associated with the progress of RIOM was further investigated

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