Southern Research, Frederick, MD, USA.
Center for Clinical Translational Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
BMC Microbiol. 2021 Mar 29;21(1):93. doi: 10.1186/s12866-021-02146-w.
Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) 1 day prior and 1 and 4 days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform.
Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Animals with diarrhea at day 4 post-irradiation, had significantly lower levels of Lentisphaere and Verrucomicrobia phyla and Bacteroides genus at baseline before irradiation, suggesting a potential association between the prevalence of microbiomes and differential susceptibility to radiation-induced diarrhea.
Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.
肠道微生物组的组成和维持对肠道内稳态至关重要。然而，人们对于大剂量辐射对肠道微生物组组成的影响知之甚少，这种大剂量辐射可能是癌症放射治疗、核事故或故意释放核或放射性武器造成的。因此，我们试图分析暴露于大剂量辐射的非人类灵长类动物（NHP）肠道微生物组的变化。我们收集了 19 只 NHP（食蟹猕猴，Macaca mulatta）在接受 7.4Gy 钴-60 伽马射线（LD）照射前 1 天、照射后 1 天和 4 天的粪便样本。从每个样本中提取 16S V4 rRNA 序列，然后使用 QIIME 平台进行生物信息学分析。
α多样性（香农多样性指数）显示照射前后无明显差异，而β多样性分析显示照射后（+4 天）微生物组与基线（照射前）相比存在显著差异。与代谢内稳态破坏相关的已知因素厚壁菌门/拟杆菌门比值从照射后暴露于辐射后的 1.2 降至小于 1。放线菌、拟杆菌、普雷沃氏菌（副拟杆菌科）和魏氏菌属的丰度增加了 2 倍以上，而不动杆菌属和气球菌属的丰度减少了 10 倍以上。52%（19/36）的辐射暴露动物在照射后第 4 天出现腹泻。比较照射后第 4 天有腹泻和无腹泻动物的粪便微生物组组成，发现与腹泻相关的乳杆菌属增加，而 Lentisphaerae 和 Verrucomicrobioa 门和拟杆菌属减少。照射后第 4 天出现腹泻的动物在照射前基线时 Lentisphaere 和 Verrucomicrobia 门和 Bacteroides 属水平显著降低，表明微生物组的流行与对辐射诱导性腹泻的不同易感性之间存在潜在关联。
我们的研究结果表明，NHP 肠道微生物组组成在辐射损伤后发生了实质性改变，并深入了解了全身大剂量辐射暴露后的早期变化。未来的研究将有助于确定辐射暴露的微生物组生物标志物，并开发有效的治疗干预措施来减轻辐射损伤。
