甲亢患者肠道微生态的特征

目的 探讨甲亢患者肠道菌群的特征。方法 以15例甲亢患者作为甲亢组,15例健康志愿者作为对照组。采用Illumina Miseq高通量测序平台对甲亢组和对照组新鲜粪便样本中所有细菌的16S rRNA (16S ribosome RNA)-V3区进行DNA测序,分析操作分类单元(operational taxonomic units,OTU)数量,分析肠道菌群物种的丰度,并进行聚类分析和代谢通路相关性分析。结果 样本稀疏曲线表明测序深度充分,物种多样性分析显示OTU值为24 578,微生物丰度较高,测序覆盖深度(Coverage指数)>0.99。与对照组相比,在属水平,甲亢组肠道菌群的3个丰度指数(Ace、Sobs和Chao)均低于对照组(P<0.05),2个多样性指数(Shannon和Simpson)分别低于和高于对照组(P<0.05)。30份样品共检测到13个菌门,均以厚壁菌门、拟杆菌门、放线菌门和变形菌门占优势,差异无统计学意义。在属水平,共检测到246种菌群,对照组含有51种特有菌群,而甲亢患者肠道菌群种类显著减少,仅含有7种特有肠道菌群。甲亢组的直肠真杆菌属丰度明显低于对照组(P<0.05),ROC曲线的曲线下面积(area under the curve,AUC)为0.72。在同与免疫有关的功能代谢的相关性分析中,发现直肠真杆菌属与上皮细胞的细菌侵入这一代谢通路呈负相关(r=-0.367,P=0.046)。结论 甲亢患者肠道菌群的丰度和多样性下降,直肠真杆菌属是甲亢患者区别于健康人的明显差异菌,直肠真杆菌属丰度的降低可能与甲亢免疫机制相关。菌群的定量分析可能早期预测甲亢。

Characteristics of gut microbiota in patients with hyperthyroidism

Objective To investigate the characteristics of gut microbiota in patients with hyperthyroidism. Methods Fifteen patients with hyperthyroidism were served as study group, and 15 healthy volunteers were served as control group. The Illumina Miseq high-throughput sequencing platform was used to analyze DNA sequencing of the 16S rRNA-V3 region of all bacteria in the fresh faecal samples from the patients and controls, the number of operational taxonomic units (OTUs) and the abundance of gut microbiota species were analyzed. Cluster analysis and metabolic pathway correlation analysis were also conducted. Results The sample rarefaction curve showed that the sequencing depth was sufficient, and species diversity analysis showed that the OTU value was 24 578. The microbial abundance was high, and the Coverage index >0.99. The three abundance indexes (Ace, Sobs, and Chao) of the gut microbiota in the hyperthyroidism group were lower than those in the control group (P<0.05). And the two diversity indices (Shannon and Simpson) were lower and higher than the control group respectively (P<0.05). A total of 13 phyla were detected in 30 samples, all of which were dominated by Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria, the difference was not statistically significant. At the genus level, a total of 246 species of bacteria were detected. The control group contained 51 species of endemic bacteria, while the gut microbiota species of the patients had a significant decrease, with only 7 specific species. The abundance of gut microbiota in the hyperthyroidism group was significantly lower than that in the control group (P<0.05), and the AUC of ROC was 0.72. In the correlation analysis with immunologically related functional metabolism, it was found that Eubacterium rectale group was negatively correlated with the metabolic pathway of bacterial invasion of epithelial cells (r=-0.367, P=0.046). Conclusions The abundance and diversity of gut microbiota in patients with hyperthyroidism are decreased. Eubacterium rectale group can significantly distinguish the patients with hyperthyroidism from healthy people. The decrease in the abundance of Eubacterium rectale group may be related to the immune mechanism of hyperthyroidism. Quantitative analysis of the bacteria is possible to predict hyperthyroidism at early stage.