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Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats

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Robin Mesnage, Maxime Teixeira, Daniele Mandrioli, Laura Falcioni, Mariam Ibragim, Quinten Raymond Ducarmon, Romy Daniëlle Zwittink, Caroline Amiel, Jean Michel Panoff, Emma Bourne, Emanuel Savage, Charles A. Mein, Fiorella Belpoggi, Michael N. Antoniou

Original languageEnglish
Article number471
JournalCommunications Biology
Volume4
Issue number1
DOIs
PublishedDec 2021

Bibliographical note

Funding Information: This work was funded by the Sustainable Food Alliance (USA), and in part by the Franciscan Health Foundation (USA) and the Sheepdrove Trust (UK), whose support is gratefully acknowledged. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

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.

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