AUTHOR=Wang Yan , Li Jiatong , Zhang Haonan , Zheng Xin , Wang Jiantao , Jia Xiaoyue , Peng Xian , Xie Qian , Zou Jing , Zheng Liwei , Li Jiyao , Zhou Xuedong , Xu Xin 

TITLE=Probiotic Streptococcus salivarius K12 Alleviates Radiation-Induced Oral Mucositis in Mice

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.684824

DOI=10.3389/fimmu.2021.684824

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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. Here, we evaluated the treatment outcome of probiotic <italic>Streptococcus salivarius</italic> K12 on RIOM mice, and oral microbiota that is associated with the progress of RIOM was further investigated.</p></sec><sec><title>Methods</title><p>An experimental RIOM mouse model was established, and <italic>S. salivarius</italic> 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 <italic>S. salivarius</italic> K12. The oral microbiota of mice was further analyzed by 16S rRNA sequencing, microbial culture and qPCR.</p></sec><sec><title>Results </title><p>Irradiation induced conspicuous mucositis in the oral cavity of mice. <italic>S. salivarius</italic> 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. <italic>S. salivarius</italic> K12 treatment reconstituted the oral microbiota and decreased the abundance of oral anaerobes of RIOM mice. In addition, <italic>S. salivarius</italic> K12 treatment inhibited NI1060 in <italic>Pasteurella</italic> genus and downregulated the expression of nitrate reductase.</p></sec><sec><title>Conclusions</title><p><italic>S. salivarius</italic> K12 treatment can alleviate RIOM and reconstituted the dysbiotic oral microbiota in mice. <italic>S. salivarius</italic> K12 may represent a promising adjuvant treatment to improve the quality of life of cancer patients receiving radiotherapy.</p></sec>