南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (3): 358-369.doi: 10.12122/j.issn.1673-4254.2021.03.07

• • 上一篇    下一篇

2型糖尿病与肠道核心菌群的相关性

肖 瑶，牛 玥，毛明慧，林 涵，汪佰丽，乌恩奇，赵焕虎，李树春   

  • 出版日期:2021-03-20 发布日期:2021-04-06

Correlation analysis between type 2 diabetes and core gut microbiota

  • Online:2021-03-20 Published:2021-04-06

RichHTML

55

PDF

782

摘要： 目的 分析2型糖尿病(T2D)患者和正常人群肠道菌群种类、丰度和结构差异，探讨肠道菌群变化与T2D的相关性。方法 收集133例临床粪便样本(健康样本78例，T2D病例样本55例)，应用Hiseq2500对16 s rRNA基因的V3+V4区进行高通量测序，下机数据用Usearch、QIIME进行数据的拼接过滤，分类并进行物种注释。利用R语言数据包进行样品Alpha多样性指数，样品Beta多样性指数分析，比较样本菌群丰富度和多样性。比较正常组与T2D组的菌群差异，并在矫正相关因素后筛选疾病标志菌群。采用PICRUST软件进行差异菌群功能预测。结果 两组菌群在多样性上存在显著差异。聚类分析表明厚壁菌门和拟杆菌门是门分类上的差异优势物种。LefSe分析表明，两组在2个门、3个纲、3个目、4个科、10个属的相对丰度存在显著差异。在校正相关因素影响后，筛选出T2D相关菌群标志物可能为Bifidobacterium、Bifidobacteriales、Bifidobacteriaceae、Actinobacteria、Bacilli、Lactobacillales、Lactobacillaceae、Lactobacillus。在此基础上，通过差异菌群进行KEGG代谢通路分析发现组间36条KEGG代谢通路存在显著差异，T2D组的柠檬酸循环、脂多糖生物合成等代谢途径均有上调。结论 T2D组和正常组肠道菌群在组成和丰度上都存在差异，T2D组明显显示出生态失调的特点。

关键词: 2型糖尿病；肠道菌群；16S rRNA；代谢通路

Abstract: Objective To analyze the species, abundance and structure differences of intestinal flora between patients with type 2 diabetes mellitus (T2D) and healthy individuals and explore the correlation between intestinal flora changes and T2D. Methods We collected a total of 133 clinical fecal samples from 78 healthy individuals and 55 patients with T2D. Hiseq2500 was used for high-throughput sequencing of the V3+V4 regions of the 16S rRNA gene. Usearch and QIIME were used for data splicing and filtering, classification and species annotation. The Alpha diversity index and Beta diversity index of the samples were analyzed using R language data packets to compare the richness and diversity of the sample flora. The flora differences were compared between the two groups and the disease marker flora was screened after correction of the relevant factors. PICRUST software was used to predict the function of different flora. Results There was significant difference in the intestinal flora diversity between the two groups. Cluster analysis showed that Fimicutes and Bacteroidetes were the dominant species at the phylum level. LefSe analysis showed that significant differences in the relative abundance between the two groups in 2 phyla, 3 classes, 3 orders, 4 families and 10 genera. After correction for the influence of related factors, the markers of T2Drelated bacteria groups were identified, including Bifidobacterium, Bifidobacteriales, Bifidobacteriaceae, Actinobacteria, Bacilli, Lactobacillales, Lactobacillaceae and Lactobacillus. On this basis, analysis of KEGG metabolic pathways of the differential flora revealed significant differences in 36 KEGG metabolic pathways between the two groups, and the citric acid cycle, lipopolysaccharide biosynthesis and other metabolic pathways were all up-regulated in T2D group. Conclusion The composition and abundance of intestinal flora were different between T2D group and the normal group, and T2D group showed the characteristics of ecological imbalance.

Key words: type 2 diabetes mellitus; intestinal flora; 16S rRNA; metabolic pathways