Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism.

Autor: Fu K; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Chen X; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Shou N; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Wang Z; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Yuan X; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Wu D; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Wang Q; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Cheng Y; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Ling N; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China., Shi Z; State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2023 Jan 25; Vol. 71 (3), pp. 1758-1767. Date of Electronic Publication: 2023 Jan 13.
DOI: 10.1021/acs.jafc.2c08519
Abstrakt: Swainsonine induced liver inflammation in livestock; however, the underlying mechanisms, especially the role of bile acids (BAs), in the pathogenesis remained elusive. Here, our results showed that swainsonine induced hepatic inflammation via changing BA metabolism and gut microbiota in mice. Swainsonine significantly upregulated the levels of deoxycholic acid (DCA) and taurine-β-muricholic acid (T-β-MCA) in the serum and liver of mice due to the markedly increased genus Clostridium and the decreased genus Lactobacillus in the gut. As antagonists of the farnesoid X receptor (FXR), elevated DCA and T-β-MCA inhibited hepatic Fxr gene expression and thus suppressed FXR-SHP signaling and activated hepatic Cyp7a1 gene expression, which induced a significant upregulation of the total BA level in serum, contributing to liver inflammation. These findings offer new insights into the underlying mechanisms in which swainsonine induced liver inflammation in mice via the gut-liver axis and suggest that gut microbiota and its metabolite BAs may be underlying triggering factors.
Databáze: MEDLINE
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