Creatine-mediated ferroptosis inhibition is involved in the intestinal radioprotection of daytime-restricted feeding
Yingjuan He,
Gaomei Zhao,
Xue Ouyang,
Shaobo Wang,
Yin Chen,
Chenwenya Li,
Yongwu He,
Jining Gao,
Songling Han,
Jinghong Zhao,
Junping Wang,
Cheng Wang
Affiliations
Yingjuan He
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Gaomei Zhao
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Xue Ouyang
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Shaobo Wang
Department of Nephrology, Xinqiao Hospital, Army Medical University, Chongqing, China
Yin Chen
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Chenwenya Li
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Yongwu He
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Jining Gao
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Songling Han
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Jinghong Zhao
Department of Nephrology, Xinqiao Hospital, Army Medical University, Chongqing, China
Junping Wang
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Cheng Wang
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Army Medical University, Chongqing, China
Ionizing radiation-induced intestinal injury (IRIII) is a catastrophic disease lack of sufficient medical countermeasures currently. Regulation of the gut microbiota through dietary adjustments is a potential strategy to mitigate IRIII. Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention with pleiotropic health benefits. Whether this dietary pattern influences the pathogenesis of IRIII remains vague. We evaluated the impact of TRF on intestinal radiosensitivity in this study and discovered that only daytime TRF (DTRF), not nighttime TRF, could ameliorate intestinal damage in mice that received a high dose of IR. Faecal metagenomic and metabolomic studies revealed that the intestinal creatine level was increased by approximate 9 times by DTRF, to which the Bifidobacterium pseudolongum enrichment contribute. Further investigations showed that creatine could activate the energy sensor AMP-activated protein kinase in irradiated enterocytes and induce phosphorylation of acetyl-CoA carboxylase, resulting in reduced production of polyunsaturated fatty acids and reduced ferroptosis after IR. The administration of creatine mitigated IRIII and reduced bacteremia and proinflammatory responses. Blockade of creatine import compromised the ferroptosis inhibition and mitigation of DTRF on IRIII. Our study demonstrates a radioprotective dietary mode that can reshape the gut microbiota and increase intestinal creatine, which can suppress IR-induced ferroptosis, thereby providing effective countermeasures for IRIII prevention.
