Ochratoxin A induces abnormal tryptophan metabolism in the intestine and liver to activate AMPK signaling pathway

Journal of Animal Science and Biotechnology

Research

Shuangshuang Zhai¹  Deqin Xiao²  Weiqing Ma³  Wence Wang³  Shanshan Zhu³  Lin Yang³  Yongwen Zhu³  Yang Fu³  Lukuyu Ben⁴  Michel Dione⁵  Daiyang Xia⁶ 

[1] College of Animal Science, YangtzeUniversity, 434025, Jingzhou, China;College of Mathematics and Informatics, South China Agricultural University, 510642, Guangzhou, China;Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China;Int Livestock Res Inst, 00100, Nairobi, Kenya;Int Livestock Res Inst, 24265, Dakar, Senegal;School of Marine Sciences, Sun Yat-Sen University, and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), 519082, Zhuhai, China;

关键词: AMPK;    Metabolomics;    Ochratoxin A;    Tryptophan metabolism;   

DOI  :  10.1186/s40104-023-00912-6

 received in 2023-03-11, accepted in 2023-07-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOchratoxin A (OTA) is a mycotoxin widely present in raw food and feed materials and is mainly produced by Aspergillus ochraceus and Penicillium verrucosum. Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder, especially Bacteroides plebeius (B. plebeius) overgrowth. However, whether OTA or B. plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown. This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver.Materials and methodsA total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups. The control group was given 0.1 mol/L NaHCO3 solution, and the OTA group was given 235 μg/kg body weight OTA for 14 consecutive days. Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics. AMPK-related signaling pathway factors were analyzed by Western blotting and mRNA expression.ResultsMetabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intestinal nicotinuric acid levels, the downstream product of tryptophan metabolism, which were significantly negatively correlated with B. plebeius abundance. In contrast, OTA induced a significant increase in indole-3-acetamide levels, which were positively correlated with B. plebeius abundance. Simultaneously, OTA decreased the levels of ATP, NAD+ and dipeptidase in the liver. Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine, anthranilic acid and nicotinic acid. Moreover, OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein.ConclusionOTA decreased the level of nicotinuric acid in the intestinal tract, which was negatively correlated with B. plebeius abundance. The abnormal metabolism of tryptophan led to a deficiency of NAD+ and ATP in the liver, which in turn activated the AMPK signaling pathway. Our results provide new insights into the toxic mechanism of OTA, and tryptophan metabolism might be a target for prevention and treatment.Graphical Abstract

【 授权许可】

CC BY   
© Chinese Association of Animal Science and Veterinary Medicine 2023

【 图 表 】

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