Characteristics of Intestinal Microflora in Patients with Coronary Heart Disease
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摘要:
目的 分析云南冠心病人群肠道菌群结构和多样性特征，探究不同类型冠心病人群之间，及与无冠脉病变人群肠道菌群结构差异。 方法 共采集急性心肌梗死患者67名（A组）、不稳定型心绞痛患者91名（B组）、稳定型心绞痛患者47名（C组）、冠脉无异常者64名（D组）、冠状动脉粥样硬化患者37名（E组），提取粪便DNA，根据细菌16srRNA v3-v4序列设计特异性引物，进行PCR扩增，使用Illumina HiSeq PE250进行测序，测序结果进行物种组成统计，Alpha多样性，组间差异分析，最终得到样品物种信息。 结果 各组间肠道菌群结构存在差异（P < 0.05）。与D组相比，A组的梭杆菌增多，B组的拟杆菌减少，变形杆菌、放线菌增多，C组的拟杆菌减少，变形杆菌、梭杆菌增多，E组变形杆菌增多（ P < 0.05）。Alpha多样性发现显示急性心肌梗死患者组的Alpha多样性高于其他组（ P < 0.05）。 结论 冠状动脉粥样硬化患者、稳定型心绞痛患者、不稳定型心绞痛患者、急性心肌梗死患者与对照组肠道菌群的结构、多样性不同，他们存在不同程度的肠道菌群失调。 Abstract:Objective To analyze the composition and diversity of intestinal microflora in patients with coronary heart disease in Yunnan, and to explore the differences of intestinal microflora among different types of coronary heart disease and those without coronary artery disease. Methods 67 patients with acute myocardial infarction（group A）, 91 patients with unstable angina（group B）, 47 patients with stable angina（group C）, 64 patients without abnormal coronary arteries（group D）and 37 patients with coronary atherosclerosis（group E）were enrolled. Faeces sample DNA was extracted. Specific primers were designed according to 16SrRNA v3-v4 sequence of bacteria, PCR amplification was carried out, and sequenced with Illumina hiseq PE250. The sequencing results were analyzed by species composition statistics, Alpha diversity, intergroup difference analysis, and finally get the species information of the faeces sample. Results There were differences in the composition of intestinal flora among groups（P < 0.05）. Compared with group D, there were more Clostridium in group A, less Bacteroides, more Proteus and actinomycetes in group B, less Bacteroides, more Proteus and Clostridium in group C, and more Proteus in group E（ P < 0.05）. The alpha diversity of AMI patients was higher than that of other groups（ P < 0.05）. Conclusion The composition, diversity and abundance of intestinal flora in coronary atherosclerotic group, stable angina group, unstable angina group, acute myocardial infarction group and control group were different in Yunnan, and they had intestinal flora disorder at various degrees. -
Key words:
- Coronary artery disease /
- Atherosclerosis /
- Intestinal microorganism /
- 16srRNA
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图 1 各组间门、纲、目、科属物种分类柱状图
Ⅰ：属水平物种；Ⅱ：科水平物种；Ⅲ：纲水平物种；Ⅳ：目水平物种；Ⅴ：门水平物种。
Figure 1. Bar chart of phylum，class，order，family and genus species in each group
图 2 各组间Alpha多样性比较
Ⅰ：Observed species多样性比较，*P < 0.05，**P < 0.01，***P < 0.001；Ⅱ：Simpson多样性比较，*P < 0.05，**P < 0.01，***P < 0.001。
Figure 2. Alpha diversity comparison among groups
表 1 五组间一般临床检测资料
$ \left( {{{\bar x}} \pm {{s}}} \right)$ Table 1. General clinical examination data of five groups
$ \left( {{{\bar x}} \pm {{s}}} \right)$ 组别 男性
n（%）年龄
（岁）BMI
（kg/m2）空腹血糖
（mmol/L）cTnI TG
（mmol/L）LDL-C
（mmol/L）ALT
（U/L）Cr
（μmol/L）高血压
n（%）糖尿病
n（%）A 61（91.0） 57.13 ± 12.36 24.94 ± 3.01 6.55 ± 2.74 17.17 ± 24.89 1.80 ± 0.11 2.83 ± 0.77 40.15 ± 20.61 71.12 ± 24.98 31（46.3）# 12（17.9） B 48（60.0）* 62.43 ± 9.95 24.79 ± 3.40 6.32 ± 2.81 0.01 ± 0.06* 1.94 ± 1.23 2.55 ± 1.21 29.84 ± 14.53 65.39 ± 15.79 50（62.5）# 19（23.8） C 23（52.3）* 58.43 ± 9.69 24.34 ± 3.46 5.96 ± 2.37 0.01 ± 0.029* 1.78 ± 0.91 2.78 ± 0.78 27.76 ± 14.39* 68.00 ± 18.41 19（43.2）# 11（25.0） D 18（35.3）* 53.92 ± 12.63∆ 23.52 ± 3.32 5.56 ± 1.33 0.00 ± 0.00* 1.49 ± 0.73 2.65 ± 0.86 26,48 ± 15.04* 60.33 ± 13.52* 17（33.3）#∆ 6（11.8） E 18（62.1）* 63.86 ± 8.72▲ 24.48 ± 3.31 5.90 ± 2.31 0.00 ± 0.00* 1.69 ± 0.89 2.42 ± 0.88 27.79 ± 17.93* 66.29 ± 14.31 21（72.4）* 6（20.7） 与A组相比，*P < 0.05；与E组相比 #P < 0.05；与B组相比 ∆P < 0.05；与D组相比 ▲P < 0.05。 
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表 2 差异显著物种列表
Table 2. List of species with significant difference（Genus Level）
物种名称 A组（均值） B组（均值） C组（均值） D组（均值） E组（均值） P g__Acinetobacter 5.31E-05 3.17E-04 1.04E-03 1.03E-05 1.56E-05 0.01 g__Akkermansia 2.68E-03 5.39E-04 2.48E-03 5.92E-03 3.61E-03 4.51E-04 g__Alistipes 0.03 0.02 0.01 0.01 9.33E-03 2.39E-05 g__Anaerofustis 0 0 1.76E-06 0 4.47E-06 0.04 g__Anaerotruncus 1.58E-04 9.54E-05 7.74E-05 3.20E-04 1.81E-04 2.85E-03 g__Atopobium 2.07E-04 6.63E-05 2.99E-04 3.62E-05 4.69E-05 9.73E-04 g__Bilophila 4.71E-03 1.75E-03 1.25E-03 5.45E-03 1.28E-03 3.09E-05 g__Clostridium XI 1.82E-03 8.87E-03 7.20E-03 8.41E-03 5.92E-03 2.42E-03 g__Clostridium XVIII 1.37E-04 1.71E-04 1.00E-03 1.96E-04 2.79E-04 4.56E-03 g__Clostridium XlVa 0.06 0.05 0.03 0.05 0.06 0.01 g__Clostridium XlVb 6.47E-03 5.16E-03 2.48E-03 5.47E-03 2.86E-03 3.44E-03 g__Clostridium sensu stricto 1.75E-03 5.10E-03 1.99E-03 3.60E-03 1.96E-03 0.02 g__Cryptobacterium 1.60E-05 2.73E-06 0 1.29E-06 4.47E-06 9.27E-03 g__Desulfovibrio 3.03E-03 1.29E-03 1.48E-03 1.15E-03 8.05E-04 0.02 g__Eikenella 1.23E-06 0 8.80E-06 0 2.23E-06 8.07E-03 g__Eisenbergiella 2.02E-03 1.12E-03 4.29E-04 7.34E-04 8.80E-04 0.01 g__Flavobacterium 0 0 1.23E-05 0 0 0.03 g__Gemella 1.10E-04 9.36E-05 2.29E-04 1.07E-04 5.14E-05 0.03 g__Gemmiger 0.03 0.02 0.04 0.02 0.02 0.04 g__Granulicatella 3.01E-04 1.90E-04 4.47E-04 1.34E-04 1.56E-04 8.03E-03 g__Klebsiella 0.01 0.03 0.02 5.33E-03 3.84E-03 1.92E-03 g__Lactobacillus 4.16E-03 9.76E-03 0.03 3.07E-03 0.01 4.18E-03 g__Megamonas 0.02 0.05 0.02 0.04 0.01 0.01 g__Odoribacter 2.34E-03 1.66E-03 5.49E-04 1.25E-03 7.04E-04 4.06E-04 g__Oscillibacter 3.73E-03 3.04E-03 1.38E-03 2.57E-03 1.45E-03 2.58E-04 g__Parabacteroides 0.02 0.01 0.01 0.02 0.02 1.65E-04 g__Paraprevotella 7.95E-03 5.86E-03 3.33E-03 6.34E-03 3.21E-03 0.05 g__Porphyromonas 6.66E-05 5.27E-05 6.51E-05 2.33E-05 4.92E-05 0.02 g__Propionibacterium 3.70E-06 9.99E-06 8.80E-06 1.29E-06 0 0.04 g__Rothia 2.11E-04 7.00E-05 1.39E-04 7.23E-05 1.85E-04 0.01 g__Ruminococcus 0.03 0.02 0.02 0.01 0.02 0.02 g__Streptococcus 0.02 8.37E-03 0.02 0.01 0.01 2.95E-05 g__Veillonella 6.73E-03 0.01 0.02 5.63E-03 0.03 8.24E-04
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