Warm water enriches gut symbiotic <em>Lactobacillus johnsonii</em> to alleviate radiation-induced intestinal toxicity

Food as medicine offers a promising strategy for disease intervention. Preferences for drinking water at different temperatures may influence disease occurrence, development and treatment outcomes including cancer therapy. Radiotherapy-induced gastrointestinal (GI) syndrome narrows the therapeutic window and degrades the life quality of patients. In this study, we demonstrated that drinking warm water mitigated radiation-induced GI injury in mouse models. 16S rRNA gene sequencing showed that warm water preserved the gut microbiota and enriched symbiotic <em>Lactobacillus johnsonii</em>, which could alleviate intestinal radiation toxicity alone and generate synergistic radioprotective effect when combined with warm water consumption. Warm water elevated rectal temperature in irradiated mice, and exposure to higher ambient temperature accelerated the proliferation of <em>L. johnsonii</em>. Untargeted metabolomics and prokaryotic transcriptome sequencing analyses validated the alterations in physiological function of <em>L. johnsonii</em> under higher ambient temperature, particularly augmenting the purine biosynthesis. Blockage of purine production attenuated the radioprotective property of <em>L. johnsonii</em>. Together, our findings highlight the beneficial effect of warm water on radiotherapy-induced GI syndrome, underscore the gut symbiotic <em>L. johnsonii</em> as a candidate probiotic for use in food manufacturing to combat intestinal radiation injury.