Oral colon-retentive inulin gels protect against radiation-induced hematopoietic and gastrointestinal injury by improving gut homeostasis.

Ionizing radiation-induced injury often occurs in nuclear accidents or large-dose radiotherapy, leading to acute radiation syndromes characterized by hematopoietic and gastrointestinal injuries even to death. However, current radioprotective drugs are only used in hospitals with unavoidable side effects. Here, we heated the aqueous solution of inulin, a polysaccharide dietary fiber, forming colon-retentive gel as a radiation protector in radiotherapy. Mouse models were established after Co γ-ray irradiation of the total body or abdomen. Inulin gels were orally administered to the mice every day from 3 days pre-radiation to 3 days post-radiation. The hematopoietic system was well protected with good blood cell recovery and cell proliferation in the femur and spleen. Oral inulin gels increased the relative abundances of key commensal microorganisms including f_Lachnospiraceae, Akkermansia, Blautia, and short-chain fatty acids (SCFAs) metabolites. The secretion of the anti-inflammation cytokines IL-22 and IL-10 in the intestinal cells also increased. Similarly, the expression of the tight junction proteins claudin-1 and occludin in the gut mucosa was affected. In an orthotopic murine colorectal cancer model, oral inulin gels followed by 10-Gy abdomen radiation improved the radiotherapy efficiency with low attenuated radiation injury. Taken the data together, these results suggest that oral inulin gels are a bioactive material against ionizing radiation-induced injury.