鞣花酸在UM-A型人肠道菌群中体外转化及对肠道菌群的影响

Biotransformation of ellagic acid by gut microbiota from urolithin metabotype A and its effect on gut microbiota in vitro

采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive Orbitrap/MS)对鞣花酸在尿石素代谢型A(urolithin metabotype A,UM-A)人肠道菌群中体外代谢转化产物进行定性定量分析,并应用16S rRNA高通量测序技术分析鞣花酸对人肠道菌群组成及代谢通路的影响。在人肠道菌群孵育后,鞣花酸主要转化产物为尿石素M6、尿石素C、尿石素A。代谢转化24 h,产物尿石素M6、尿石素C和尿石素A的生成率分别为18.36%、1.23%和43.45%;代谢转化72 h,尿石素A生成率为52.09%。与空白组相比,在门水平上鞣花酸显著增加厚壁菌门相对丰度,显著降低拟杆菌门、变形菌门相对丰度;在属水平上显著增加粪球菌属(Coprococcus)、丁酸弧菌(Anaerostipes)、瘤胃球菌属(Ruminococcus)、毛螺杆菌属(Lachnospira)和迟缓埃格特菌属(Eggerthella)等相对丰度。肠道菌群KEGG代谢通路分析显示鞣花酸下调了脂多糖生物合成蛋白、脂肪细胞因子信号通路、碳水化合物消化吸收等代谢通路的丰度;上调了RIG-I样受体信号通路,电子转运载体等代谢通路的丰度。该研究为鞣花酸对UM-A代谢型人群健康作用的物质基础和肠道菌群调节作用提供基础数据。

In order to discover the metabolic pathway of ellagic acid(EA)in human gut microbiota of urolithin metabotype A(UM-A),the metabolites of EA were identified and quantified by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)via intestinal bacteria incubation model.Moreover,the effects of EA on the composition and metabolic pathway of human gut microbiota were analyzed by 16S rRNA high-throughput sequencing.The results showed that urolithin M6,urolithin C,urolithin A were the main metabolites of EA after incubated with UM-A human gut microbiota in vitro.The generation rate of urolithin M6,urolithin C and urolithin A was 18.36%,1.25%,and 43.45%at 24 h,respectively.At the period of 72 h incubation,the total generation rate of urolithin A was 52.09%.Compared with the control group,EA significantly increased the relative abundance of Firmicutes and decreased the relative abundance of Bacteroidetes and Proteobacteria at phylum level.In addition,the relative abundance of Coprococcus,Anaerostipes,Ruminococcus,Lachnospira,and Eggerthella significantly increased at genus level.KEGG metabolic pathway analysis suggested that EA group showed increased enrichment in pathways such as lipopolysaccharide biosynthesis,adipocytokine signaling pathway,carbohydrate digestion and absorption,whereas it showed decreased enrichment in pathways such as RIG-I-like receptor signaling pathway and electron transfer carriers.This study provides basic data for the determination of the material basis and gut microbiota regulation of EA′s health effects on UM-A population.