杨淑惠, 李成曦, 李建萍, 王雨萌, 刘云, 段金廒, 郭建明. 基于肠道菌群测序及非靶向脂质组学分析黄蜀葵花对炎症性肠病小鼠菌群稳态及脂质代谢的影响J. 药学学报, 2022, 57(12): 3546-3556. DOI: 10.16438/j.0513-4870.2022-0706
引用本文: 杨淑惠, 李成曦, 李建萍, 王雨萌, 刘云, 段金廒, 郭建明. 基于肠道菌群测序及非靶向脂质组学分析黄蜀葵花对炎症性肠病小鼠菌群稳态及脂质代谢的影响J. 药学学报, 2022, 57(12): 3546-3556. DOI: 10.16438/j.0513-4870.2022-0706
YANG Shu-hui, LI Cheng-xi, LI Jian-ping, WANG Yu-meng, LIU Yun, DUAN Jin-ao, GUO Jian-ming. Regulatory effect of Flos Abelmoschus manihot in mice with inflammatory bowel disease based on gut microbiota sequencing and untargeted lipidomicsJ. Acta Pharmaceutica Sinica, 2022, 57(12): 3546-3556. DOI: 10.16438/j.0513-4870.2022-0706
Citation: YANG Shu-hui, LI Cheng-xi, LI Jian-ping, WANG Yu-meng, LIU Yun, DUAN Jin-ao, GUO Jian-ming. Regulatory effect of Flos Abelmoschus manihot in mice with inflammatory bowel disease based on gut microbiota sequencing and untargeted lipidomicsJ. Acta Pharmaceutica Sinica, 2022, 57(12): 3546-3556. DOI: 10.16438/j.0513-4870.2022-0706

基于肠道菌群测序及非靶向脂质组学分析黄蜀葵花对炎症性肠病小鼠菌群稳态及脂质代谢的影响

Regulatory effect of Flos Abelmoschus manihot in mice with inflammatory bowel disease based on gut microbiota sequencing and untargeted lipidomics

  • 摘要: 本研究旨在探讨黄蜀葵花对慢性炎症性肠病(inflammatory bowel disease, IBD) 模型小鼠的改善作用, 并分析其对IBD模型小鼠肠道菌群结构及粪便中脂质轮廓的影响。所有动物福利和实验过程均遵循南京中医药大学动物伦理委员会的规定。采用葡聚糖硫酸钠(DSS) 诱导慢性IBD小鼠模型, 评价小鼠体重变化、疾病活动指数、结肠组织病理损伤以及结肠中炎症因子的基因表达水平。采集各组小鼠的粪便样品, 进行Illumina高通量测序, 检测肠道菌群丰度; 采用基于超高效液相色谱-高分辨串联质谱的非靶向脂质组学, 检测粪便中脂质含量。结果显示, IBD模型小鼠体重显著降低, 结肠出现明显炎症反应, 主要表现为结肠组织病理损伤及炎症因子的基因表达上调。黄蜀葵花给药后可显著恢复IBD模型小鼠的体重, 改善结肠组织病理损伤, 降低结肠中炎症因子的基因水平。肠道菌群测序结果显示, IBD模型小鼠肠道菌群的物种多样性和丰富度降低, 疣微菌门细菌丰度显著增加, 拟杆菌门细菌丰度显著降低; 黄蜀葵花可恢复IBD模型小鼠肠道菌群的丰富度及多样性, 增加各级类群物种数量, 恢复拟杆菌门细菌丰度。粪便非靶向脂质组学分析结果发现, IBD模型小鼠的鞘脂及甘油磷脂代谢通路变化最为显著。黄蜀葵花可抑制鞘脂代谢通路中神经酰胺及鞘磷脂的合成, 显著抑制甘油磷脂代谢通路中醚键连接的磷脂酰胆碱及醚键连接的磷脂酰乙醇胺的合成, 增加磷脂酰乙醇胺的含量。综上所述, 黄蜀葵花可有效改善慢性IBD模型小鼠的疾病状况, 具有调控肠道菌群稳态及脂质代谢的作用, 两者之间的相关机制有待深入探讨。

     

    Abstract: In this study, the ameliorative effects of Flos Abelmoschus manihot on mice with chronic inflammatory bowel disease (IBD) were investigated and its effects on the structure of the intestinal flora as well as the lipid profile in feces of IBD mice were analyzed. All animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese medicine. A mouse model with chronic IBD induced by dextran sulfate sodium (DSS) was used to evaluate changes in body weight, disease activity index (DAI), colonic histopathological damage as well as gene expression levels of inflammatory factors in the colon. Fecal samples from mice in each group were collected and subjected to Illumina high-throughput sequencing to detect the abundance of intestinal flora; samples were analyzed by UHPLC-Q-Exactive® HF Quadrupole-Orbitrap® of untargeted lipidomics, which detects lipid content in feces. Administration of Flos Abelmoschus manihot could significantly restore the body weight and ameliorate colonic histopathological damage in IBD mice. Sequencing of the gut microbiota revealed that the species diversity and richness of the gut microbiota in IBD mice were decreased, with a significant increase in the abundance of Verrucomicrobia and a significant decrease in the abundance of Bacteroidetes; Flos Abelmoschus manihot significantly increased the richness and diversity of intestinal microbiota in IBD mice, increased the number of taxa species at each level, and restored the abundance of bacteria in the phylum Bacteroidetes. Analysis of fecal lipid profiles identified the most significant changes in sphingolipid and glycerophospholipid metabolic pathways in IBD mice, with Flos Abelmoschus manihot inhibiting ceramide and sphingomyelin synthesis in sphingolipid metabolism. In summary, Flos Abelmoschus manihot can effectively improve the disease condition of mice with chronic IBD, and it has the effect of regulating intestinal flora homeostasis and lipid metabolism, but the related mechanism between the two still needs to be deeply explored.

     

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