Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis

Roseburia
DOI: 10.1016/j.celrep.2024.113846 Publication Date: 2024-02-26T12:45:12Z
ABSTRACT
The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates tumoricidal effects radiation and degrades intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) gastrointestinal tract. Oral gavage R. assembles at site synthetizes butyrate, sensitizing to alleviating intestinal toxicity primary hepatic metastasis mouse models. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing patients with rectal cancer, facilitating radiogenic autophagy cells. OR51E1 shows positive correlation RALB tissues model. Blockage OR51E1/RALB signaling restrains butyrate-elicited irradiated Our findings highlight gut commensal bacteria motivates radiation-induced accelerate cell death through butyrate/OR51E1/RALB axis provide promising radiosensitizer for pre-clinical setting.
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