Abstract:
Approximately 60-80% of cancer patients treated with abdominopelvic radiotherapy suffer post-radiotherapy toxicities including radiation enteropathy and myelosuppression. Effective preventive and therapeutic strategies are lacking for such radiation injury. The gut microbiota holds high investigational value for deepening our understanding of the pathogenesis of radiation injury, especially radiation enteropathy which resembles inflammatory bowel disease pathophysiology and for facilitating personalized medicine by providing safer therapies tailored for cancer patients. Preclinical and clinical data consistently support that gut microbiota components including lactate-producers, SCFA-producers, indole compound-producers and Akkermansia impose intestinal and hematopoietic radio-protection. These features serve as potential predictive biomarkers for radiation injury, together with the microbial diversity which robustly predicts milder post-radiotherapy toxicities in multiple types of cancer. The accordingly developed manipulation strategies including selective microbiota transplantation, probiotics, purified functional metabolites and ligands to microbe-host interactive pathways are promising radio-protectors and radio-mitigators that merit extensive validation in clinical trials. With massive mechanistic investigations and pilot clinical trials reinforcing its translational value the gut microbiota may boost the prediction, prevention and mitigation of radiation injury. In this review, we summarize the state-of-the-art landmark researches related with radio-protection to provide illuminating insights for oncologists, gastroenterologists and laboratory scientists interested in this overlooked complexed disorder.
摘要:
大约60-80%的接受腹骨盆放射疗法治疗的癌症患者遭受放射疗法后的毒性,包括放射性肠病和骨髓抑制。对于这种辐射损伤缺乏有效的预防和治疗策略。肠道微生物群对于加深我们对辐射损伤发病机理的理解具有很高的研究价值,特别是放射性肠病,它类似于炎症性肠病的病理生理学,并通过为癌症患者提供更安全的治疗来促进个性化医疗。临床前和临床数据一致支持肠道微生物群成分,包括乳酸生产者,SCFA生产者,吲哚化合物生产者和Akkermansia施加肠道和造血放射性保护。这些特征可作为辐射损伤的潜在预测生物标志物,与微生物多样性一起,这有力地预测了多种类型癌症的放疗后毒性。相应开发的操作策略,包括选择性微生物群移植,益生菌,纯化的功能性代谢物和微生物-宿主相互作用途径的配体是有前途的放射保护剂和放射缓解剂,值得在临床试验中进行广泛验证。随着大规模的机械研究和初步临床试验加强其转化价值,肠道微生物群可能会提高预测,预防和减轻辐射伤害。在这次审查中,我们总结了与无线电保护相关的最先进的里程碑研究,为肿瘤学家提供启发性的见解,胃肠病学家和实验室科学家对这种被忽视的复杂疾病感兴趣。