砷的环境相关水平对肠道微生物组及其功能宏基因组的影响。

The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome.

机构信息

Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27519.

Department of Molecular and Cellular Biology, NIH West Coast Metabolomics Center, University of California, Davis, Davis, California 95616.

出版信息

Toxicol Sci. 2017 Dec 1;160(2):193-204. doi: 10.1093/toxsci/kfx174.

Abstract

Multiple environmental factors induce dysbiosis in the gut microbiome and cause a variety of human diseases. Previously, we have first demonstrated that arsenic alters the composition of the gut microbiome. However, the functional impact of arsenic on the gut microbiome has not been adequately assessed, particularly at environmentally relevant concentrations. In this study, we used 16S rRNA sequencing and metagenomics sequencing to investigate how exposure to 100 ppb arsenic for 13 weeks alters the composition and functional capacity of the gut microbiome in mice. Arsenic exposure altered the alpha and beta diversities as well as the composition profile of the gut microbiota. Metagenomics data revealed that the abundances of genes involved in carbohydrate metabolism, especially pyruvate fermentation, short-chain fatty acid synthesis, and starch utilization, and were significantly changed. Moreover, lipopolysaccharide biosynthesis genes, multiple stress response genes, and DNA repair genes were significantly increased in the gut microbiome of arsenic-exposed mice. The genes involved in the production or processing of multiple vitamins, including folic acid and vitamins B6, B12, and K2, were also enriched in arsenic-treated mice. In, addition, genes involved in multidrug resistance and conjugative transposon proteins were highly increased after treatment with arsenic. In conclusion, we demonstrate that arsenic exposure, at an environmentally relevant dose, not only perturbed the communal composition of the gut microbiome but also profoundly altered a variety of important bacterial functional pathways.

摘要

多种环境因素会导致肠道微生物组失调,并引发多种人类疾病。此前,我们首次证明砷会改变肠道微生物组的组成。然而,砷对肠道微生物组的功能影响尚未得到充分评估,特别是在与环境相关的浓度下。在这项研究中,我们使用 16S rRNA 测序和宏基因组测序来研究暴露于 100ppb 砷 13 周如何改变小鼠肠道微生物组的组成和功能能力。砷暴露改变了 alpha 和 beta 多样性以及肠道微生物群的组成谱。宏基因组学数据显示,参与碳水化合物代谢的基因,特别是丙酮酸发酵、短链脂肪酸合成和淀粉利用的基因,丰度显著改变。此外,砷暴露小鼠肠道微生物组中的脂多糖生物合成基因、多种应激反应基因和 DNA 修复基因显著增加。参与多种维生素(包括叶酸以及维生素 B6、B12 和 K2)产生或加工的基因在砷处理的小鼠中也富集。此外,砷处理后,与多药耐药和转座子蛋白相关的基因高度增加。总之,我们证明了在环境相关剂量下暴露于砷不仅会扰乱肠道微生物组的群落组成,还会深刻改变多种重要的细菌功能途径。

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