Blood bacterial DNAemia is associated to serum zonulin level in older subjects. Blood bacterial DNAemia

Background: Several studies in the last decade suggested the existence of a richmicrobiota in human bloodstream. Assuming that increased presence of bacteria inblood can represent a significant factor in the development and progression of agingassociated diseases, here we performed the quantification and the taxonomic profilingof the bacterial DNA in blood samples collected from a group of forty-four oldersubjects enrolled in a nursing home. Metabolic and functional markers were alsomeasured and used to evaluate possible associations with bacterial DNA.Results: qPCR analysis revealed that all the older volunteers harbored detectableamounts of bacterial DNA in their blood. 16S rRNA gene profiling showed that thebacterial DNA detected in blood was mostly ascribable to the Gram-negative phylumProteobacteria. Furthermore, whereas the taxonomic structure was quite similar (with apredominance of Pseudomonadaceae and Enterobacteriaceae), the total amount ofbacterial DNA varied considerably between subjects. Correlation analyses revealedthat the bacterial DNA detected in blood (both as overall DNA load and DNAconcentration of specific bacterial taxa) correlated with several host parameters thatare markers for intestinal permeability, immune response, kidney and liver function,and insulin sensitivity. Particularly, we found a significant correlation between theamount of circulating bacterial DNA and zonulin serum levels, an emerging marker ofintestinal permeability.Conclusions: In this study, we report for the first time that older individuals harbordetectable amounts of bacterial DNA in blood. The correlation with zonulin levelssuggests that para-cellular permeability of epithelial and endothelial cell layers mayplay an important role in bacterial migration into the bloodstream. These findings leadus to speculate that the bacterial DNA detected in blood is indicative of a bloodmicrobiota that may influence several aspects of host physiology as well as thedevelopment and prognosis of diseases in older subjects.

研究背景：近十年的多项研究表明，人体血流中存在丰富的微生物群（microbiota）。鉴于血液中细菌丰度升高可能是衰老相关疾病发生与进展的重要影响因素，本研究对养老院招募的44名老年受试者的血液样本进行了细菌DNA定量分析与分类学特征分析。同时检测代谢与功能标志物，用于评估其与血液细菌DNA的潜在关联。
研究结果：实时荧光定量聚合酶链反应（qPCR）分析显示，所有老年受试者血液中均可检测到细菌DNA。16S rRNA基因（16S rRNA gene）测序分析表明，血液中检测到的细菌DNA主要隶属于革兰氏阴性菌门（Gram-negative phylum）下的变形菌门（Proteobacteria）。此外，尽管血液菌群的分类学结构较为相似（以假单胞菌科（Pseudomonadaceae）和肠杆菌科（Enterobacteriaceae）为主），但不同受试者的血液细菌DNA总含量差异显著。相关性分析显示，血液中检测到的细菌DNA（包括总DNA载量与特定细菌类群的DNA浓度）与多项宿主参数存在相关性，这些参数涵盖肠道通透性、免疫应答、肝肾功能以及胰岛素敏感性标志物。尤为重要的是，本研究发现循环细菌DNA总量与血清连蛋白（zonulin）水平存在显著相关性，而连蛋白是一种新兴的肠道通透性标志物。
研究结论：本研究首次报道，老年个体血液中可检测到细菌DNA。其与连蛋白水平的相关性提示，上皮与内皮细胞层的细胞旁通透性可能在细菌迁移入血的过程中发挥重要作用。上述发现促使我们推测，血液中检测到的细菌DNA提示存在血液微生物群，该菌群可能影响宿主生理的多个方面，以及老年个体疾病的发生与预后。