Tissular Genomic Responses to Oral FB1 Exposure in Pigs.

Léonie Dopavogui,Joëlle Laffite,Isabelle P Oswald,Jean-Denis Bailly,Arnaud Polizzi,Nicolas Loiseau,Philippe Pinton,Anne Fougerat,Olivier Puel,Claire Naylies,Hervé Guillou,Wendy Klement,Yannick Lippi,Chloé Terciolo,Pascal Gourbeyre,Anne-Marie Cossalter

doi:10.3390/toxins14020083

Abstract

Fumonisin B1 (FB1) is a widespread mycotoxin produced by fungal Fusarium species—mainly in maize, one of the plants most commonly used for food and feed. Pigs and horses are the animal species most susceptible to this mycotoxin. FB1 exposure can cause highly diverse clinical symptoms, including hepatotoxicity, immunotoxicity, and intestinal barrier function disturbance. Inhibition of ceramide synthetase is a well-understood ubiquitous molecular mechanism of FB1 toxicity, but other more tissue-specific effects remain to be elucidated. To investigate the effects of FB1 in different exposed tissues, we cross-analyzed the transcriptomes of fours organs: liver, jejunum, jejunal Peyer’s patches, and spleen. During a four-week study period, pigs were fed a control diet or a FB1-contaminated diet (10 mg/kg feed). In response to oral FB1 exposure, we observed common biological processes in the four organs, including predominant and recurrent processes (extracellular matrix organization, integrin activation, granulocyte chemotaxis, neutrophil migration, and lipid and sterol homeostasis), as well as more tissue-specific processes that appeared to be related to lipid outcomes (cell cycle regulation in jejunum, and gluconeogenesis in liver).

Highlights

Fusarium spp. is among the most frequent fungal genus found on different cereal crops and causes dramatic economic losses and food safety concerns due to reduced cereal yield and quality [1]
When focusing on genes regulated with a fold change (FC) greater than 1.5, Fumonisin B1 (FB1) exposure induced significant upregulation of 538 genes in jejunum, 241 in liver, 123 in Peyer’s patches, and 33 in spleen; and significant downregulation of 715 genes in jejunum, 194 in liver, 62 in Peyer’s patches, and 73 in spleen
When comparing the significance and the level of gene induction observed in each tissue, the liver and jejunum responded to FB1 exposure with a higher fold change in gene expressions and stronger evidence compared to the spleen, which exhibited the most strongly downregulated genes, and the Peyer’s patches, which showed more moderate responses

Summary

Introduction

Fusarium spp. is among the most frequent fungal genus found on different cereal crops and causes dramatic economic losses and food safety concerns due to reduced cereal yield and quality [1]. Climate change has led to shifts in temperature and humidity weather conditions, which have favored Fusarium dissemination [2]. The variability in Fusarium spp. incidence generates a remodeling spectrum of mycotoxin exposure and a significant increase in cereal contamination, with potentially enhanced impacts on human and animal health. Contrasting weather conditions during cereal growing periods favor the proliferation of F. verticillioides and F. proliferatum. Global warming causes stronger climatic contrasts, which will likely lead to more frequent findings of high fumonisin concentrations in maize in temperate regions [3]. Since 2007, the European Union has set recommendations and regulations for the maximum level of the sum of fumonisins B1

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Conclusion