摘要
目的:探讨脓毒症合并心功能障碍患者的肠道微生态组成及多样性改变情况。方法:本研究共纳入39例受试者，其中健康受试者13例（A组），脓毒症不合并心功能障碍者12例（B组），脓毒症合并心功能障碍者14例（C组）。入组当天完成血液和粪便标本采集以及超声心动图检查。检测并记录受试者的心肌肌钙蛋白T（cTnT）、人心型脂肪酸结合蛋白（HFABP）、氨基末端B型利钠肽（NT-proBNP）、左心室射血分数（LVEF）及降钙素原（PCT）水平。采用16S核糖体DNA（rDNA）测序对粪便中的菌群进行多样性分析，并比较各组间的菌群组成。结果:3组受试者cTnT、HFABP、NT-proBNP、LVEF及PCT水平比较，差异均有统计学意义（H = 33.279、24.748、28.694、26.552、27.032，P均<0.001）。进一步两两比较发现，与B组相比较，C组患者cTnT、HFABP、NT-proBNP水平更高，而LVEF更低（P均<0.05）。Alpha多样性分析显示，3组受试者肠道菌群丰富度[Chao1指数及基于丰度的覆盖估计值（ACE）]、多样性（香农指数及辛普森指数）比较，差异均有统计学意义（H = 13.761、13.761、19.189、15.536，P均<0.05），且B、C两组肠道菌群丰富度、多样性均显著低于A组，C组肠道菌群多样性更低（P均<0.05）。Beta多样性分析显示，A、B、C组受试者肠道菌物种相似度比较，差异均有统计学意义[0.239（0.147，0.332）、0.001 （-0.164，0.049）、-0.212（-0.315，0.040），H = 22.599，P = 0.001]，且B、C两组肠道菌群物种相似度与A组比较，差异均有统计学意义（P均<0.05）。3组受试者肠道微生物群中，梭状芽孢杆菌纲、芽孢杆菌纲、瘤胃球菌科、毛螺菌科、瘤胃球菌属及未定位的毛螺菌属细菌的相对丰度比较，差异均有统计学意义（H = 23.918、22.794、17.265、16.846、11.862、16.846，P均<0.05）。B、C组的梭状芽孢杆菌纲、瘤胃球菌科、毛螺菌科、瘤胃球菌属及未定位的毛螺菌属相对丰度均显著低于A组，且C组梭状芽孢杆菌纲、瘤胃球菌科、毛螺菌科的相对丰度更低（P均<0.05）；B、C组芽孢杆菌的相对丰度均明显高于A组，且C组更高（P均<0.05）。结论:脓毒症合并心功能障碍患者的心肌损伤标志物水平显著增高，同时肠道微生态多样性显著下降，主要表现为梭状芽孢杆菌、瘤胃球菌科及毛螺菌科细菌相对丰度减少，而芽孢杆菌的相对丰度增加。
Abstract
Objective:To preliminarily clarify the changes of intestinal microecological composition and diversity in patients with sepsis-induced myocardial dysfunction.Methods:A total of 39 subjects were enrolled in this study, including 13 healthy subjects (group A), 12 septic patients without myocardial dysfunction (group B) and 14 patients with sepsis-induced myocardial dysfunction (group C). Blood and feces samples were collected and echocardiography was performed on the day of enrollment. The cardiac troponin T (cTnT), human heart-type fatty acid binding protein (HFABP), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF) and procalcitonin (PCT) were determined and recorded. The 16S ribosomal DNA (rDNA) sequencing was used to determine the bacterial sequence in the feces, and the composition of microflora among the three groups was compared.Results:The levels of cTnT, HFABP, NT-proBNP, LVEF and PCT among the three groups all showed significant differences (H = 33.279, 24.748, 28.694, 26.552, 27.032; all P < 0.001). Further pairwise comparison found that compared with the group B, the levels of cTnT, HFABP and NT-proBNP in the group C were much higher, while the LVEF level was much lower (all P < 0.05). Alpha diversity analysis showed that the richness [Chao1 index and abundance-based coverage estimator (ACE)] and diversity (Shannon index and Simpson index) of bacterial flora among the three groups all showed significant differences (H = 13.761, 13.761, 19.189, 15.536; all P < 0.05). The richness and diversity of bacterial flora in groups B and C were much lower than those in the group A, and the diversity of bacterial flora in the group C was lowest (all P < 0.05). Beta diversity analysis showed that the similarities of bacterial flora among the three groups all showed significant differences [0.239 (0.147, 0.332), 0.001 (-0.164, 0.049), -0.212 (-0.315, 0.040); H = 22.599, P = 0.001]. The similarities of bacterial flora in groups B and C were statistically significantly different as compared with the group A (both P < 0.05). At the three levels of class, family and genus, the relative abundance of Clostridia, Bacillus, Ruminococcaceae, Lachnospiracea, Ruminococcus and Lachnospiracea_incertae_sedis among the three groups all showed significant differences (H = 23.918, 22.794, 17.265 16.846, 11.862, 16.846; all P < 0.05). The relative abundance of Clostridia, Ruminococcaceae, Lachnospiracea, Ruminococcus and Lachnospiracea_incertae_sedis in groups B and C was much lower than that in the group A, and the relative abundance of Clostridia, Ruminococcaceae and Lachnospiracea in the group C was lowest (all P < 0.05). The relative abundance of Bacillus in groups B and C was much higher than that in the group A, and it was highest in the group B (all P < 0.05).Conclusion:The levels of myocardial injury biomarkers are increased and the diversity of intestinal microbiome is decreased significantly in patients with myocardial dysfunction induced by sepsis, which mainly shows as reduced abundance of Clostridia, Ruminococcaceae and Lachnospiracea, together with increased abundance of Bacillus.
基金项目
浙江省基础公益研究计划项目(LGF18H150010)
万方数据