T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

Institute of Animal Husbandry and Veterinary Sciences Hubei Academy of Agricultural Sciences Wuhan 430064 China

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing China

Monogastric Research Center School of Agriculture and Environment Massey University Palmerston North 4442 New Zealand

State Key Laboratory of Agricultural Microbiology Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province Hubei Hongshan Laboratory Frontiers Science Center for Animal Breeding and Sustainable Production College of Animal Sciences and Technology Huazhong Agricultural University Wuhan 430070 Hubei China

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