Integrated transcriptomics and metabolomics reveal the mechanism of intestinal damage upon acute patulin exposure in mice

• Published in: Ecotoxicology and environmental safety 2024-05, Vol.276, p.116270-116270, Article 116270
• Main Authors: Zhang, Ting, Yan, Min, Chang, Min, Hou, Xiaohui, Wang, Furong, Song, Wei, Wang, Yuan, Feng, Kewei, Yuan, Yahong, Yue, Tianli
• Format: Article
• Language: English
• Subjects: Damage mechanism; Intestinal injury; Metabolic pathways; Multi-omics integration; Patulin exposure; Toxin products
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116270

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT. [Display omitted] •The small intestinal injury symptoms induced by PAT were more severe than colon.•Genes dose-dependently altered in the small intestine and fluctuated in the colon.•Phospholipids were dose-dependently accumulated after acute PAT exposure.•Amino acid, nucleotide, and lipid metabolic pathways were affected.•PAT reached the stomach and small intestine but cannot reach the colon.