Phytate enhances gut Parasutterella colonization to alleviate radiation injury

Food as medicine shows promise for disease intervention or treatment. Here, we found phytate, an active ingredient of plant-based diets, exhibits properties in mitigating radiotherapy-related complications. Oral gavage of phytate restored hematogenic organ atrophy, elevated peripheral blood neutrophils and white blood cells, reduced inflammation, and improved gastrointestinal (GI) integrity in irradiated mice. Phytate intake modulated the gut microbiota, facilitating the colonization of symbiotic Parasutterella in GI tract, thus combating intestinal radiation toxicity. In vitro assays and untargeted metabolomics identified 3-phenyllactic acid (PLA) and N-acetyl-L-leucine (NL) as functional metabolites produced by Parasutterella. In vitro, ex vivo, and in vivo models showed that PLA induces M2-like polarization in macrophages, while NL reduced oxidative stress, both counteracting radiation toxicity and working synergistically. Our findings offer mechanistic insights into phytate for alleviating radiation-associated complications and suggest that Parasutterella and its metabolites might be employed as promising probiotics or postbiotics for cancer patients undergoing radiotherapy.