Fu Keyi, Shou Na, Yuan Xuefeng, Xu Wenqian, Wu Dandan, Wang Qi, Gu Lijun, Zeng Yanjun, Li Yanzhong, Shi Zunji
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.
J Agric Food Chem. 2024 Jun 7. doi: 10.1021/acs.jafc.4c02243.
Liver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus alleviating inflammation and genus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.
苦马豆素可引发家畜肝脏炎症，影响农牧业发展。我们之前的研究表明胆汁酸（BAs）在苦马豆素诱导的肝脏炎症中起重要作用。然而，其发病机制，特别是肝脏和血清代谢物综合谱以及微生物衍生的吲哚代谢物的作用尚未阐明。本研究旨在通过结合靶向500代谢组学和吲哚代谢物定量分析，阐明产吲哚细菌和吲哚代谢物与苦马豆素诱导的肝脏炎症之间的联系机制。苦马豆素显著扰乱了小鼠的肝脏和血清代谢组。减轻炎症的菌属和产生吲哚代谢物的菌属显著减少。吲哚乙酸（IAA）是本研究中唯一减少的芳烃受体（AHR）配体。类似地，一些导致肝脏损伤的细菌显著增加。这些发现表明，产吲哚细菌和吲哚代谢物可能是苦马豆素诱导肝脏炎症的潜在触发因素。
