Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Vaiomer, Department of Research and Development, Bioinformatics Division, Labège, France.
Clin J Am Soc Nephrol. 2019 May 7;14(5):692-701. doi: 10.2215/CJN.12161018. Epub 2019 Apr 8.
The association between gut dysbiosis, high intestinal permeability, and endotoxemia-mediated inflammation is well established in CKD. However, changes in the circulating microbiome in patients with CKD have not been studied. In this pilot study, we compare the blood microbiome profile between patients with CKD and healthy controls using 16S ribosomal DNA sequencing.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Blood bacterial DNA was studied in buffy coat samples quantitatively by 16S PCR and qualitatively by 16S targeted metagenomic sequencing using a molecular pipeline specifically optimized for blood samples in a cross-sectional study comparing 20 nondiabetic patients with CKD and 20 healthy controls.
There were 22 operational taxonomic units significantly different between the two groups. 16S metagenomic sequencing revealed a significant reduction in diversity (Chao1 index) in the CKD group compared with healthy controls (127±18 versus 145±31; =0.04). Proteobacteria phylum, Gammaproteobacteria class, and Enterobacteriaceae and Pseudomonadaceae families were more abundant in the CKD group compared with healthy controls. Median 16S ribosomal DNA levels did not significantly differ between CKD and healthy groups (117 versus 122 copies/ng DNA; =0.38). GFR correlated inversely with the proportion of Proteobacteria (=-0.54; ≤0.01).
Our pilot study demonstrates qualitative differences in the circulating microbiome profile with lower diversity and significant taxonomic variations in the blood microbiome in patients with CKD compared with healthy controls.
肠道菌群失调、肠道通透性增加和内毒素血症介导的炎症与 CKD 密切相关。然而，CKD 患者循环微生物组的变化尚未得到研究。在这项初步研究中，我们使用 16S 核糖体 DNA 测序比较了 CKD 患者和健康对照者的血液微生物组图谱。
设计、设置、参与者和测量：通过 16S PCR 对血液细菌 DNA 进行定量研究，通过专门针对血液样本优化的分子流水线进行 16S 靶向宏基因组测序进行定性研究，在一项横断面研究中比较了 20 例非糖尿病 CKD 患者和 20 例健康对照者。
两组之间有 22 个操作分类单位存在显著差异。16S 宏基因组测序显示，与健康对照组相比，CKD 组的多样性（Chao1 指数）显著降低（127±18 对 145±31；=0.04）。与健康对照组相比，CKD 组中厚壁菌门、γ变形菌纲、肠杆菌科和假单胞菌科更为丰富。CKD 组和健康组之间 16S 核糖体 DNA 水平无显著差异（117 对 122 拷贝/ng DNA；=0.38）。GFR 与变形菌门的比例呈负相关（=-0.54；≤0.01）。
我们的初步研究表明，与健康对照组相比，CKD 患者的循环微生物组图谱存在定性差异，血液微生物组的多样性降低，分类学变化显著。
