Hydrogen-Rich Water Attenuates Radiation-Induced Oral Mucositis in Mice via Antioxidant and Gut Microbiota-Stabilizing Effects: A Longitudinal Study

Radiation induced oral mucositis (RIOM) frequently complicates head and neck radiotherapy, leading to severe pain, compromised nutrition, and often requiring treatment modifications. Although craniofacial only irradiation is confined to the head and neck region, it can still disrupt gut homeostasis. Mice subjected to head and neck irradiation developed marked epithelial damage in both the oral and intestinal mucosa, as evidenced by pronounced RIOM and diminished barrier integrity. Histological examination revealed substantial mucosal thinning and leukocyte infiltration in the tongue, along with reduced occludin and ZO1 expression in colonic tissues. Supplementation with hydrogen-rich water (HW) markedly lowered the severity of oral lesions and preserved epithelial thickness, while restoring the expression of tight junction proteins in colon. Fecal 16S rRNA sequencing showed that radiation alone provoked expansions of Streptococcus and Helicobacter, coupled with a decline in short chain fatty acid producing families (Lachnospiraceae, Ruminococcaceae). In contrast, HW supplementation partially reversed these microbial shifts, correlating with reduced oral inflammatory markers. Collectively, these findings underscore an oral gut axis whereby HW fosters mucosal healing through microbiome stabilization and decreased inflammatory stress, suggesting HW as a promising adjunct for managing head and neck irradiation related complications.