Aflatoxin B 1 -induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: The roles of pipecolic acid and norepinephrine.

Autor: Ye L; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China; Research and Development Center, Guangdong Marubi Biotechnology Co., Ltd., 510700 Guangzhou, China., Chen H; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China., Wang J; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China., Tsim KWK; Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China., Wang Y; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China., Shen X; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China., Lei H; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China; Guangdong Laboratory for Lingnan Modern Agriculture, 510642 Guangzhou, China; Heyuan Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 517000 Heyuan, China. Electronic address: hongtao@scau.edu.cn., Liu Y; Guangdong Provincial Key Laboratory of Food Quality and Safety / National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 510642 Guangzhou, China; Guangdong Laboratory for Lingnan Modern Agriculture, 510642 Guangzhou, China; Heyuan Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 517000 Heyuan, China. Electronic address: liuyunle@scau.edu.cn.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Aug 05; Vol. 474, pp. 134822. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1016/j.jhazmat.2024.134822
Abstrakt: The disturbed gut microbiota is a key factor in activating the aflatoxin B 1 (AFB 1 )-induced liver pyroptosis by promoting inflammatory hepatic injury; however, the pathogen associated molecular pattern (PAMP) from disturbed gut microbiota and its mechanism in activating liver pyroptosis remain undefined. By transplanting AFB 1 -originated fecal microbiota and sterile fecal microbial metabolites filtrate, we determined the association of PAMP in AFB 1 -induced liver pyroptosis. Notably, AFB 1 -originated sterile fecal microbial metabolites filtrate were more active in triggering liver pyroptosis in mice, as compared to parental fecal microbiota. This result supported a critical role of the metabolic homeostasis of gut microbiota in AFB 1 -induced liver pyroptosis, rather than an injurious response to direct exposure of AFB 1 in liver. Among the gut-microbial metabolites, pipecolic acid and norepinephrine were proposed to bind TLR4 and NLRP3, the upstream proteins of pyroptosis signaling pathway. Besides, the activations of TLR4 and NLRP3 were linearly correlated with the concentrations of pipecolic acid and norepinephrine in the serum of mice. In silenced expression of TLR4 and NLRP3 in HepG2 cells, pipecolic acid or norepinephrine did not able to activate hepatocyte pyroptosis. These results demonstrated the necessity of gut microbial metabolism in sustaining liver homeostasis, as well as the potential to provide new insights into targeted intervention for AFB 1 hepatotoxicity.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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