Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2024-01-01 Epub Date: 2024-07-07 DOI:10.1080/19490976.2024.2374608
Sen Li, Yuwei Cai, Tong Guan, Yu Zhang, Kai Huang, Ze Zhang, Wangqing Cao, Xiao Guan
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Abstract

With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aβ and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aβ and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.

奎宁酸通过肠道微生物色氨酸代谢产物抑制DR3/IKK/NF-κB信号传导,从而缓解高脂饮食诱发的神经炎症。
随着人口老龄化和高脂肪饮食(HFD)的增加,阿尔茨海默病(AD)的发病率急剧上升。氧化应激和神经炎症是阿尔茨海默病发病机制的两大标志,因此天然抗氧化剂在预防阿尔茨海默病方面具有广阔的前景。在这里,我们研究发现,从小米中提取的一种多酚--奎宁酸(QA)能显著降低高密度脂蛋白胆固醇(HFD)诱导的脑氧化应激和神经炎症以及Aβ和p-Tau的水平。对肠道微生物群的研究表明,QA 治疗后,HFD 小鼠肠道微生物群的组成得到了改善。代谢组分析表明,QA能显著增加肠道微生物色氨酸代谢物吲哚-3-乙酸(IAA)和犬尿氨酸(KYNA)。此外,IAA和KYNA与促炎因子和AD指标呈负相关。在HFD小鼠身上进行的进一步实验证明,IAA和KYNA能再现QA抑制大脑氧化应激和炎症反应、降低Aβ和p-Tau水平的作用。服用IAA后大脑的转录组学分析表明,IAA抑制了DR3/IKK/NF-κB信号通路。总之,这项研究表明,QA可以通过肠道微生物色氨酸代谢产物调节炎症性DR3/IKK/NF-κB信号通路,从而抵消HFD诱导的脑氧化应激和神经炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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