Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.
Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.
复制标题
肾功能受损和肠道菌群失调导致慢性肾病患者三甲胺-N-氧化物增加
DOI：
10.1038/s41598-017-01387-y
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发表时间：
2017-05-03
影响因子：
4.6
通讯作者：
Yin J
中科院分区：
文献类型：
--
作者：
Xu KY;Xia GH;Lu JQ;Chen MX;Zhen X;Wang S;You C;Nie J;Zhou HW;Yin J
慢性肾脏疾病（CKD）患者患心血管疾病（cvd）的风险增加。本研究旨在通过动物实验研究中国CKD患者肠道菌群和血液三甲胺- n -氧化物浓度（TMAO），并探讨其可能的解释。CKD患者血浆TMAO中位数为30.33 μmol/L，显著高于健康对照组的2.08 μmol/L。下一代测序显示CKD患者肠道微生物群明显失调，细菌多样性减少，群落结构偏倚。CKD患者来自γ -变形菌门的机会致病菌百分比较高，而有益微生物（如玫瑰菌、粪球菌和瘤胃球菌科）的百分比较低。PICRUSt分析显示，CKD患者中涉及胆碱、甜菜碱、左旋肉碱和三甲胺（TMA）代谢的8个基因发生了改变。此外，我们将CKD患者和健康对照的粪便样本转移到抗生素治疗的C57BL/6小鼠中，发现接受CKD患者肠道微生物的小鼠血浆TMAO水平明显高于对照组，肠道微生物群的组成也不同。我们目前的研究表明，由于肾功能受损和肠道微生物群失调，CKD患者血浆TMAO水平升高。
Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such asRoseburia,Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.