首页|京大戟醋制调节双歧杆菌-短链脂肪酸代谢改善肠毒性作用研究

京大戟醋制调节双歧杆菌-短链脂肪酸代谢改善肠毒性作用研究

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为探索京大戟醋制调节肠道菌群减轻肠道毒性的作用机制,寻找与醋制减毒相关的关键菌群并验证其功能.该研究采用衍生化方法对京大戟醋制前后粪便中的短链脂肪酸含量进行检测,结合前期肠道菌群测序结果,通过相关性分析的方法寻找与短链脂肪酸含量相关的关键菌群.通过单菌移植实验明确关键菌群调节短链脂肪酸代谢改善京大戟肠道毒性的作用,进一步将粪便提取物加入到Caco-2和RAW264.7细胞共培养体系中,以肠道紧密连接蛋白和炎症因子为指标评价其毒性差异;同时通过短链脂肪酸受体阻断剂的应用,明确短链脂肪酸在京大戟醋制降低肠道毒性中发挥的作用.研究结果显示,京大戟醋制后可以改善生品诱导的短链脂肪酸含量下降,通过相关性分析发现双歧杆菌与乙酸、丙酸、异丁酸、正丁酸、异戊酸、正戊酸的含量呈正相关.单菌移植结果显示,双歧杆菌能够改善京大戟生品导致的短链脂肪酸含量下降,提高紧密连接蛋白的表达并减轻肠道炎症反应;细胞实验结果同样证实,双歧杆菌移植后的粪便提取物能够减轻炎症反应,并提高肠上皮细胞紧密连接蛋白的表达;通过游离脂肪酸受体-2抑制剂GLPG0974的应用,证实这种改善作用与短链脂肪酸通路相关.该研究表明双歧杆菌是京大戟醋制降低肠道毒性的关键菌群,醋制后双歧杆菌丰度增高,提高肠道中短链脂肪酸含量,抑制肠道炎症反应并提高肠道紧密连接蛋白的表达从而改善京大戟的肠道毒性.
Regulation of Bifidobacterium-short chain fatty acid metabolism and improvement of intestinal toxicity of vinegar-processed Euphorbiae Pekinensis Radix
To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity,this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions.Using a derivatization method,the study measured the content of short-chain fatty acids (SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix.Combined with the results of previous gut microbiota sequencing,correlation analysis was used to identify key microbial communities related to SCFAs content.Through single-bacterium transplantation experiments,the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified.Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells,and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators.Additionally,the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix.The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material.Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid,propionic acid,isobutyric acid,n-butyric acid,isovaleric acid,and n-valeric acid.Results from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix,enhance the expression of tight junction proteins,and reduce intestinal inflammation.Similarly,cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells.The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway.This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix.Vinegar-processing increases the abundance of Bifidobacterium,elevates the intestinal SCFAs content,inhibits intestinal inflammation,and enhances the expression of tight junction proteins,thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.

Euphorbiae Pekinensis Radixdetoxification with vinegar processinginflammationBifidobacteriumshort-chain fatty acids

叶凌俊、徐晓芬、陈赛雅、张欢、干宜喧、孟涛、丁锐、李婧、曹岗、王奎龙

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浙江中医药大学药学院,浙江杭州 311400

京大戟 醋制减毒 炎症 双歧杆菌 短链脂肪酸

2024

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子:1.718
ISSN:1001-5302
年,卷(期):2024.49(23)