Abstract:
Gut microbiota (GM) is a crucial underlying player during sepsis pathogenesis. However, the causal relationship is unclear and remains to be determined. A two-sample Mendelian randomization study was implemented. The statistical data about sepsis together with GM summarized from genome-wide association studies were evaluated. Instrumental variables were defined as single-nucleotide polymorphisms with prominent correlations with exposure. The inverse-variance-weighted test was employed as a major approach of Mendelian randomization analysis to estimate of causal relationships. The inverse-variance-weighted analysis results demonstrated that at different taxa levels, Actinobacteria and Bifidobacteriaceae influence sepsis. Actinobacteria had negative relationships to sepsis risk at the phylum (β = -0.34, SE = 0.10, p = 0.0008) and class (β = -0.23, SE = 0.07, p = 0.0011) levels in outcome coded ieu-b-69. Actinobacteria at the phylum level (β = -0.22, SE = 0.10, p = 0.027) was also negatively associated with sepsis in outcome coded ieu-b-4980. Bifidobacteriaceae at the order (β = -0.20, SE = 0.06, p = 0.0021), family (β = -0.20, SE = 0.06, p = 0.0021), and genus (β = -0.20, SE = 0.06, p = 0.0007) levels were all negatively correlated with the risk of sepsis in outcome coded ieu-b-69. The results of the Wald ratio model showed that Tyzzerella genus (OR (95%CI) = 0.6902[0.4907,0.9708], p = 0.0331) and Gastranaerophilales order (OR (95%CI) = 0.5907[0.3516,0.9926], p = 0.0468) were negatively connected with sepsis. This study implied at different taxa levels Actinobacteria and Bifidobacteriaceae, Tyzzerella genus, and Gastranaerophilales order have a causal relationship with sepsis, indicating that they are protective factors for the incidence of sepsis.
摘要:
肠道菌群(GM)是脓毒症发病过程中的关键潜在参与者。然而,因果关系尚不清楚,尚待确定.实施了双样本孟德尔随机化研究。评估了来自全基因组关联研究的关于脓毒症和GM的统计数据。仪器变量被定义为与暴露具有显著相关性的单核苷酸多态性。逆方差加权检验被用作孟德尔随机化分析的主要方法,以估计因果关系。逆方差加权分析结果表明,在不同的分类单元水平上,放线菌和双歧杆菌科影响败血症。放线菌与结果编码ieu-b-69的门(β=-0.34,SE=0.10,p=0.0008)和类别(β=-0.23,SE=0.07,p=0.0011)水平的败血症风险呈负相关。在编码ieu-b-4980的结果中,门水平的放线菌(β=-0.22,SE=0.10,p=0.027)也与脓毒症呈负相关。双歧杆菌科的顺序(β=-0.20,SE=0.06,p=0.0021),家族(β=-0.20,SE=0.06,p=0.0021),和属(β=-0.20,SE=0.06,p=0.0007)水平均与编码ieu-b-69的结果中的败血症风险呈负相关。Wald比率模型的结果表明,Tyzzerella属(OR(95CI)=0.6902[0.4907,0.9708],p=0.0331)和嗜血碳菌顺序(OR(95CI)=0.5907[0.356,0.9926],p=0.0468)与脓毒症呈负相关。这项研究暗示在不同的分类群水平放线菌和双歧杆菌科,Tyzzerella属,和嗜血杆菌顺序与败血症有因果关系,表明它们是脓毒症发病的保护因素。