Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings. A hydrogen-rich water solution ameliorates the damage caused by radiotherapy to the abdominal area in mice. Radiotherapy is an effective treatment for pelvic and abdominal tumors in humans, but it can damage healthy gut tissue and lead to life-threatening intestinal injuries. Ming Cui and Sai-jun Fan at the Chinese Academy of Medical Sciences in Tianjin, China, and colleagues have found that administration of purified water infused with molecular hydrogen improved gut function and the survival rate of mice after exposure to abdominal irradiation. The hydrogen-water increased the levels of the small regulatory RNA molecule microRNA-1968-5p which in turn reduced the expression of myeloid differentiation factor MyD88 and gut inflammation. Moreover, this treatment protected the intestinal bacterial composition, highlighting its therapeutic potential for alleviating radiation-induced damage as well as other forms of microbial imbalance in the gut.