糖尿病及糖尿病心血管并发症患者肠道菌群的特征

Gut microbiota in diabetic patients and diabetic patients with cardiovascular complications

摘要:

[目的]比较2型糖尿病患者、糖尿病心血管并发症患者与健康人肠道菌群差异，分析肠道菌群与血糖、血脂等临床指标的关联，探讨肠道细菌在2型糖尿病、糖尿病心血管并发症发生、发展中的作用。[方法]招募健康人251例、糖尿病心血管并发症患者160例及糖尿病患者295例，三组各随机选取30例、30例和40例，进行血液生化指标分析和肠道菌群的宏基因组检测。[结果]与健康对照组比较，糖尿病心血管并发症组和2型糖尿病组血清丙氨酸氨基转移酶、碱性磷酸酶、甘油三酯、空腹血糖、胰岛素、糖化血红蛋白指标显著升高（P<0.05）；糖尿病患者组、糖尿病心血管并发症患者组的肠道菌群α-多样性明显降低，菌群发生改变。健康对照组中大部分优势菌属来自拟杆菌门和厚壁菌门，而糖尿病心血管并发症患者组和糖尿病患者组中大部分优势菌属则来自拟杆菌门、变形菌门和放线菌门。与健康对照组相比，糖尿病心血管并发症患者组和糖尿病患者组中，厚壁菌门比例明显下降，放线菌门和变形菌门比例明显上升。种水平上，空腹血糖与黏膜乳杆菌（Lactobacillusmucosae）、大肠埃希氏菌（Escherichia coli）、脆弱拟杆菌（Bacteroidesfragilis）呈正相关，与细枝真杆菌（Eubacteriumramulus）、Roseburiainulinivorans、Roseburiahominis、挑剔真杆菌（Eubacterium eligens）、伶俐瘤胃球菌（Ruminococcuscallidus）呈负相关；低密度脂蛋白胆固醇与嵴链球菌（Streptococcuscristatus）呈正相关，与Lachnospiraceaebacterium_6_1_63FAA和淀粉乳杆菌（Lactobacillusamylovorus）呈负相关；总胆固醇与血链球菌（Streptococcussanguinis）呈正相关。[结论]2型糖尿病和糖尿病心血管并发症患者存在明显的糖脂代谢异常和肠道菌群失调，肠道菌群紊乱可能在糖尿病发病、进展过程中发挥重要作用。

Abstract:

[Objective] To explore the possible role of intestinal bacteria in the occurrence and development of type 2 diabetes mellitus (T2DM) and cardiovascular complications, we analyzed the difference of intestinal flora between T2DM patients, T2DM patients with cardiovascular complications and healthy volunteers, and the association of intestinal flora with blood glucose and blood lipid. [Methods] A total of 251 healthy controls, 160 diabetic patients with cardiovascular complications and 295 diabetic patients were collected. From each group 30, 30 and 40 subjects were randomly selected for blood biochemical index analysis and metagenome detection of intestinal flora. [Results] The levels of serum alanine aminotransferase, alkaline phosphatase, triglyceride, fasting blood glucose, insulin and glycosylated hemoglobin in diabetic cardiovascular complications group and T2DM group were significantly higher than the healthy control group (P<0.05). The α-diversity of intestinal microflora of diabetic patients and diabetic patients with cardiovascular complications was significantly decreased, and the intestinal microbial communities were unbalanced compared with that of the healthy controls. The majority of dominant bacteria in the healthy control group were from Bacteroidetes and Firmicutes, whereas the majority of dominant bacteria in the diabetic cardiovascular complications group and the diabetic patients group were from Bacteroidetes, Proteobacteria and Actinomycetes. Compared with the healthy controls, the proportion of Firmicutes was significantly decreased, and the proportions of Actinomycetes and Proteobacteria were significantly increased in the diabetic patients with cardiovascular complications and diabetic patients. At the species level, fasting blood glucose had a positive correlation with Lactobacillus mucosae, Escherichia coli and Bacteroides fragilis, and a negative correlation with Eubacterium ramulus, Roseburia inulinivorans, Roseburia hominis, Eubacterium eligens and Ruminococcus callidus, low density lipoprotein cholesterol had a positive correlation with Streptococcus cristatus and a negative correlation with Lactobacillus amylovorus, and total cholesterol had a positive correlation with Streptococcus sanguinis. [Conclusion] T2DM patients and T2DM patients with cardiovascular complications had obvious abnormal glucose and lipid metabolism and intestinal flora imbalance. Intestinal flora disorder may play an important role in the pathogenesis and progression of diabetes.