桑黄酮对靶标毛螺细菌的抑制作用与脂质代谢通路调控

Mulberrin Inhibits Lachnospira bacterium and Modulates Lipid Metabolism via Signature Metabolites

摘要:

为了阐明桑黄酮（Mulberrin，Mul）在口-胃-肠中的消化特性，及其对毛螺细菌（Lachnospira bacterium）的抑制作用和代谢调控机制。采用体外模拟消化模型结合高效液相色谱技术，定量分析桑黄酮在胃肠环境中含量及消化率；设置5个质量浓度梯度的桑黄酮对毛螺细菌进行处理，评估其剂量依赖效应；并于三个时间点采集经毛螺细菌生物转化桑黄酮后的代谢产物，利用非靶向代谢组学技术进行系统分析。桑黄酮在模拟胃环境中消化2 h后，其消化率为71.50%；在模拟肠环境中消化2 h后则完全降解（100%）；桑黄酮对毛螺细菌的抑制作用呈现显著剂量依赖性，最高质量浓度（1000 μg·mL-1）处理下其抑制率达89.35%。非靶向代谢组学分析表明，桑黄酮处理组与空白对照组（BC）间代谢谱存在显著差异，毛螺细菌可动态转化桑黄酮生成去甲氧基柔黄素B、桑黄酮K及桑醇等特征性代谢产物。桑黄酮在口-胃-肠系统中表现出梯度消化特征；其对毛螺细菌的抑制效果与浓度呈显著正相关；桑黄酮通过调控毛螺细菌丰度，诱导产生特征性代谢物，并显著调控亚油酸代谢（P<0.0001）、花生四烯酸代谢（P<0.05）及咖啡因代谢通路（P<0.05），进而调节脂质代谢稳态。该研究为开发基于黄酮类化合物的菌群靶向抗肥胖策略提供了理论基础。

Abstract:

The digestive characteristics of mulberrin (Mul) in the oral-gastrointestinal tract and its inhibitory effects on Lachnospira bacterium along with associated metabolic regulation mechanisms were elucidated in the present study. In vitro simulated digestion models coupled with high-performance liquid chromatography (HPLC) were employed to quantitatively analyze the dynamic changes and digestive rates of Mul in gastrointestinal environments. Five mass concentration gradients of Mul were administered to Lachnospira bacterium to assess dose-dependent effects. Metabolites derived from Lachnospira bacterium biotransformation of Mul were collected at three timepoints and systematically analyzed using untargeted metabolomics. After 2 h in simulated gastric conditions, 71.50% of Mul was digested, while complete degradation (100%) was observed following 2 h in simulated intestinal environments; A significant dose-dependent inhibitory effect on Lachnospira bacterium was demonstrated,with an inhibition rate of 89.35% at the highest concentration (1000 μg·mL-1); Untargeted metabolomic analysis indicateddistinct metabolic profiles between Mul-treated and blank control (BC) groups, wherein Lachnospira bacterium dynamically converted Mul into characteristic metabolites including parvisoflavone B, kuwanon K, and morusinol. It was concluded that Mul exhibiteds gradient digestion in the oral-gastrointestinal system; its inhibitory efficacy correlateds positively with concentration; Mul modulateds lipid metabolic homeostasis by regulating Lachnospira bacterium abundance, inducing characteristic metabolite production, and significantly altering linoleic acid metabolism (P<0.0001), arachidonic acid metabolism (P<0.05), and caffeine metabolism pathways (P<0.05). This investigation provideds key mechanistic insights for developing flavonoid-based microbiota-targeted anti-obesity strategies.