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Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats.
Mesnage, Robin; Teixeira, Maxime; Mandrioli, Daniele; Falcioni, Laura; Ibragim, Mariam; Ducarmon, Quinten Raymond; Zwittink, Romy Daniëlle; Amiel, Caroline; Panoff, Jean-Michel; Bourne, Emma; Savage, Emanuel; Mein, Charles A; Belpoggi, Fiorella; Antoniou, Michael N.
Afiliação
  • Mesnage R; Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, London, UK.
  • Teixeira M; UR Aliments Bioprocédés Toxicologie Environnements, EA 4651, University of Caen Normandy (UCN), Caen, France.
  • Mandrioli D; Ramazzini Institute (RI), Bologna, Italy.
  • Falcioni L; Ramazzini Institute (RI), Bologna, Italy.
  • Ibragim M; Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, London, UK.
  • Ducarmon QR; Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands.
  • Zwittink RD; Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands.
  • Amiel C; UR Aliments Bioprocédés Toxicologie Environnements, EA 4651, University of Caen Normandy (UCN), Caen, France.
  • Panoff JM; UR Aliments Bioprocédés Toxicologie Environnements, EA 4651, University of Caen Normandy (UCN), Caen, France.
  • Bourne E; Genome Centre, Barts and the London School of Medicine and Dentistry, Blizard Institute, London, UK.
  • Savage E; Genome Centre, Barts and the London School of Medicine and Dentistry, Blizard Institute, London, UK.
  • Mein CA; Genome Centre, Barts and the London School of Medicine and Dentistry, Blizard Institute, London, UK.
  • Belpoggi F; Ramazzini Institute (RI), Bologna, Italy.
  • Antoniou MN; Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, London, UK. michael.antoniou@kcl.ac.uk.
Commun Biol ; 4(1): 471, 2021 04 14.
Article em En | MEDLINE | ID: mdl-33854195
ABSTRACT
Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Praguicidas / Trato Gastrointestinal / Fígado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Commun Biol Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Praguicidas / Trato Gastrointestinal / Fígado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Commun Biol Ano de publicação: 2021 Tipo de documento: Article