Antonio Suppa1,2, Jouni Kvist3, Xiaojing Li1, Vignesh Dhandapani1, Hanan Almulla1, Antoine Y Tian4, Stephen Kissane1, Jiarui Zhou1, Alessio Perotti3, Hayley Mangelson5, Kyle Langford5, Valeria Rossi2, James B Brown6,7,8, Luisa Orsini9,10. 1. Environmental Genomics Group, School of Biosciences, the University of Birmingham, Birmingham, B15 2TT, UK. 2. Department of Chemistry, Life Sciences and Environmental Sustainability University of Parma, Department of Life Sciences, Viale Usberti, 11/A, Parma, Italy. 3. School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK. 4. Computer Science, University of Birmingham, Birmingham, UK. 5. Phase Genomics, Seattle, WA, USA. 6. Environmental Bioinformatics, Centre for Computational Biology, School of Biosciences, University of Birmingham Edgbaston, Birmingham, B15 2TT, UK. 7. Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. 8. Statistics Department, University of California, Berkeley, Berkeley, CA, 94720 USA, Preminon LLC, Rodeo, CA, 94572, USA. 9. Environmental Genomics Group, School of Biosciences, the University of Birmingham, Birmingham, B15 2TT, UK. l.orsini@bham.ac.uk. 10. Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. l.orsini@bham.ac.uk.
Abstract
BACKGROUND: 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of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests.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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking watercauses 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.
Authors: Stephanie K Bopp; Aude Kienzler; Andrea-Nicole Richarz; Sander C van der Linden; Alicia Paini; Nikolaos Parissis; Andrew P Worth Journal: Crit Rev Toxicol Date: 2019-04-01 Impact factor: 5.635
Authors: Muhammad Abdullahi; Xiaojing Li; Mohamed Abou-Elwafa Abdallah; William Stubbings; Norman Yan; Marianne Barnard; Liang-Hong Guo; John K Colbourne; Luisa Orsini Journal: Environ Sci Technol Date: 2022-09-28 Impact factor: 11.357
Authors: Renata Marino Romano; Jeane Maria de Oliveira; Viviane Matoso de Oliveira; Isabela Medeiros de Oliveira; Yohandra Reyes Torres; Paula Bargi-Souza; Anderson Joel Martino Andrade; Marco Aurelio Romano Journal: Front Endocrinol (Lausanne) Date: 2021-03-19 Impact factor: 5.555