Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.
Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.
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DOI：
10.1371/journal.pone.0169310
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Buck M
中科院分区：
文献类型：
--
作者：
Traykova D;Schneider B;Chojkier M;Buck M
最近，一个复杂的微生物组是全面的特点，在血清和腹水患者。在本研究中，我们首次研究了Child-Pugh B级队列中炎症途径和一氧化氮的诱导，以及全身血流动力学与血液微生物组的关系。我们使用肠道感染微生物DNA qPCR阵列来筛选血液中来自肠道的53种细菌DNA。使用16 S rRNA基因作为靶标，以及PCR扩增引物（基于人类微生物组计划）和水解探针检测来设计测定。使用BioZ ICG监测仪通过阻抗心动图无创测量18个全身血流动力学参数。通过测量血液细胞因子、一氧化氮RNA阵列和一氧化氮来评估炎症反应。在这一队列的血液中，我们检测到53种细菌中的19种。与对照个体相比，腹泻患者血液中的细菌种类数量显著增加（0.2+/-0.4 vs 3.1+/-2.3; 95%CI：1.3 - 4.9; P = 0.0030）。与对照受试者相比，腹泻受试者血液中的总细菌DNA也增加（0.2+/- 1.1 vs 41.8+/-132.1; 95% CI：6.0至77.2; P = 0.0022）。在心脏病队列中，心输出量增加37%，全身血管阻力降低40%（与对照受试者相比，两者均P< 0.00001）。体循环阻力与血细菌DNA含量呈负相关（-0.621; 95% CI -0.843至-0.218; P = 0.0060），血液细菌菌种数（-0.593; 95%CI-0.83至-0.175; P = 0.0095; logistic回归：卡方= 5.8877; P = 0.0152），血清一氧化氮（-0.705; 95% CI -0.881至-0.355; P = 0.0011）。一氧化氮信号通路基因家族的许多成员在糖尿病受试者中增加。我们的研究在约90%没有感染临床证据的肝硬化患者中发现了血液细菌DNA，并表明血液中细菌DNA的数量可能会刺激信号通路，包括一氧化氮，从而降低全身血管阻力并增加心输出量。
Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort. We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects. Our study identified blood bacterial DNA in ~ 90% of the cirrhotic patients without clinical evidences of infection, and suggests that the quantity of bacterial DNA in blood may stimulate signaling pathways, including Nitric Oxide, that could decrease systemic vascular resistance and increase cardiac output.