Environmental Genomics Group, School of Biosciences, the University of Birmingham, Birmingham, B15 2TT, UK.
Department of Chemistry, Life Sciences and Environmental Sustainability University of Parma, Department of Life Sciences, Viale Usberti, 11/A, Parma, Italy.
Microbiome. 2020 Dec 15;8(1):170. doi: 10.1186/s40168-020-00943-5.
Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes.
We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the "Reactome," we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling.
Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services. Video Abstract.
围绕除草剂 Roundup 的研究是 21 世纪最具争议的研究之一。科学家们提供的证据表明,除草剂致癌和其他危及生命的疾病,但业内付费的研究报告表明,除草剂对人类或动物没有不良影响。关于 Roundup 的大部分有争议的证据都源于确定化学品安全使用的方法,这种方法是由过时的毒性测试定义的。我们采用系统生物学方法对生物医学和生态模式生物水蚤进行研究,以量化草甘膦及其商业配方 Roundup 对适应性、全基因组转录和肠道微生物群的影响,充分利用水蚤的克隆繁殖。然后,我们应用基于机器学习的统计分析方法来识别和优先考虑全基因组转录和微生物组变化之间的相关性。
我们证明,在美国饮用水监管标准规定的浓度下,慢性接触生态相关浓度的草甘膦和 Roundup 会导致胚胎发育失败,引起明显的 DNA 损伤(遗传毒性),并干扰信号转导。此外,慢性接触除草剂会改变肠道微生物群的功能和组成,干扰碳和脂肪代谢以及体内平衡。使用“Reactome”,我们在整个生命之树中确定了跨物种的保守途径,这些途径可能是其他物种中 Roundup 的潜在靶标,包括肝脏代谢、炎症途径和胶原蛋白降解,这些途径负责伤口修复和组织重塑。
我们的研究结果表明,慢性接触批准的饮用水监管标准浓度的 Roundup 和草甘膦会导致胚胎发育失败,并通过直接作用于宿主分子过程和间接作用于肠道微生物群来改变关键代谢功能。生态模式生物水蚤在水生生态系统的食物网中处于中心地位,是小型脊椎动物和无脊椎动物的首选食物,也是藻类和细菌的捕食者。除草剂对这种关键物种的影响会对水生食物网产生级联效应,影响它们提供关键生态系统服务的能力。视频摘要。