Dataset Information

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

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.

INSTRUMENT(S): Q Exactive

SUBMITTER: Robin Mesnage

PROVIDER: MTBLS138 | MetaboLights | 2020-11-19

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS138	Other
	FILES	Other
	a_MTBLS138__NEG_1_Cecal_metabolite_profiling_mass_spectrometry.txt	Txt
	a_MTBLS138__NEG_1_Serum_metabolite_profiling_mass_spectrometry.txt	Txt
	a_MTBLS138__NEG_2_Cecal_metabolite_profiling_mass_spectrometry.txt	Txt

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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 R Teixeira Maxime M Mandrioli Daniele D Falcioni Laura L Ibragim Mariam M Ducarmon Quinten Raymond QR Zwittink Romy Daniëlle RD Amiel Caroline C Panoff Jean-Michel JM Bourne Emma E Savage Emanuel E Mein Charles A CA Belpoggi Fiorella F Antoniou Michael N MN

Communications biology 20210414 1

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 biochem ...[more]

PMID: 33854195

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