Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.
Front Cell Infect Microbiol. 2021 Oct 25;11:717636. doi: 10.3389/fcimb.2021.717636. eCollection 2021.
The acute radiation-induced intestinal injury (RIII) has raised much concerns and is influenced by non-cytocidal radiation effects including the perturbations in gut microbiota. Although a number of studies have reported alteration in gut microbiota following radiation, little is known about its dynamic variation in the progression of acute RIII. In this study, mouse model were treated with total body irradiation (TBI) of 0, 4, 8 and 12 Gy, and the intestinal tissues and fecal samples were collected at 6 h, 3.5 d and 7 d post radiation. We found that the intestinal injuries were manifested in a radiation dose-dependent manner. Results from gene sequencing demonstrated that the diversity of gut microbiota was not significantly affected at the prodromal stage of acute RIII, after 6 h of radiation. At the critical stage of acute RIII, after 3.5 d of radiation, the composition of gut microbiota was correlated with the radiation dose. The Pearson's correlation analysis showed that the relative abundances of phylum Proteobacteria, genera and , and species exhibited linear correlations with radiation dose. At the recovery stage of acute RIII, after 7 d of radiation, the diversity of gut microbiota decreased as a whole, among which the relative abundance of phyla Proteobacteria and Bacteroides increased, while that of phylum Tenericutes and genus decreased. The intra-gastric administration of compound probiotics for 14 days improved the survival duration of mice exposed to 9 Gy TBI, alleviated the intestinal epithelial injury and partially restored the diversity of gut microbiota. Our findings suggest that acute RIII is accompanied by the dysbiosis of gut microbiota, including its decreased diversity, reduced abundance of beneficial bacteria and increased abundance of pathogens. The gut microbiota cannot be used as sensitive biomarkers at the prodromal stage in acute RIII, but are potential biomarkers at the critical stage of acute RIII. The dysbiosis is persistent until the recovery stage of acute RIII, and interventions are needed to restore it. The administration of probiotics is an effective strategy to protect against acute RIII and subsequent dysbiosis.
急性放射性肠损伤（RIII）引起了广泛关注，其受非细胞毒性辐射效应的影响，包括肠道微生物群的紊乱。尽管许多研究报告了辐射后肠道微生物群的改变，但对于急性 RIII 进展过程中其动态变化知之甚少。在这项研究中，通过全身照射（TBI）处理小鼠模型，剂量分别为 0、4、8 和 12 Gy，并在照射后 6 h、3.5 d 和 7 d 收集肠道组织和粪便样本。我们发现，肠损伤表现出剂量依赖性。基因测序结果表明，在急性 RIII 前驱期，即照射后 6 h，肠道微生物群的多样性没有受到显著影响。在急性 RIII 的关键期，即照射后 3.5 d，肠道微生物群的组成与辐射剂量相关。Pearson 相关分析显示，门 、属 和 种的相对丰度与辐射剂量呈线性相关。在急性 RIII 的恢复期，即照射后 7 d，肠道微生物群的多样性整体下降，其中门 、属 和 的相对丰度增加，而门 、属 的相对丰度减少。连续 14 天胃内给予复方益生菌可提高 9 Gy TBI 照射小鼠的生存时间，缓解肠上皮损伤，并部分恢复肠道微生物群的多样性。我们的研究结果表明，急性 RIII 伴随着肠道微生物群的失调，包括其多样性降低、有益菌减少和致病菌增加。在急性 RIII 的前驱期，肠道微生物群不能作为敏感的生物标志物，但在急性 RIII 的关键期是潜在的生物标志物。这种失调持续到急性 RIII 的恢复期，需要进行干预以恢复。益生菌的使用是预防急性 RIII 及其随后的失调的有效策略。
