Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Environmental Health Sciences, University of Georgia, Athens, GA, 30602, USA.
Sci Rep. 2019 Mar 13;9(1):4363. doi: 10.1038/s41598-019-40776-3.
The gut microbiota critically confers various health benefits, whereas environmental chemicals can affect its constitution and functionality thereby increasing disease risk. In the present study, we aim to evaluate the toxic effects of a wildly-used herbicide 2,4-D (2,4-dichlorophenoxyacetic acid) on the gut microbiome and host using an occupationally relevant dose. A mouse model was used combined with metagenomic sequencing and metabolomic profiling to examine the alterations induced by subchronic low-dose 2,4-D exposure in fecal and plasma samples. The metagenomics results revealed a distinct gut microbial community with profound changes in diverse microbial pathways including urea degradation, amino acid and carbohydrate metabolism in 2,4-D-treated mice. Moreover, the metabolomics results revealed that the metabolic profiles in treatment group were differentiated from control group in both fecal and plasma samples. Toxic effects on the host of 2,4-D at an occupationally relevant dose were observed indicated by decreased acylcarnitine levels in plasma. These findings indicated that 2,4-D can cause toxicity and substantially impact the gut microbiome in mice at occupationally relevant doses, inferring that the relationship between environmental contaminants and microbiota is largely underestimated calling for more comprehensive consideration of the toxicity of occupational exposures.
肠道微生物群对人体健康具有重要的益处，而环境化学物质可以影响其组成和功能，从而增加疾病风险。在本研究中，我们旨在使用职业相关剂量评估一种广泛使用的除草剂 2,4-D（2,4-二氯苯氧乙酸）对肠道微生物组和宿主的毒性作用。我们使用小鼠模型结合宏基因组测序和代谢组学分析来研究亚慢性低剂量 2,4-D 暴露在粪便和血浆样本中诱导的变化。宏基因组学结果显示，在 2,4-D 处理的小鼠中，肠道微生物群落明显不同，多种微生物途径（包括尿素降解、氨基酸和碳水化合物代谢）发生了深刻变化。此外，代谢组学结果表明，在粪便和血浆样本中，处理组的代谢谱与对照组存在差异。血浆中酰基辅酶 A 水平降低表明 2,4-D 对宿主具有毒性作用。这些发现表明，2,4-D 在职业相关剂量下可导致小鼠毒性，并对肠道微生物组产生重大影响，这表明环境污染物和微生物组之间的关系在很大程度上被低估了，需要更全面地考虑职业暴露的毒性。
