慢性肾衰竭患者肠道菌群变化及其与肾功能的相关性

Changes in intestinal flora and its correlation with renal function in chronic renal failure patients

目的研究慢性肾衰竭(CRF)患者的肠道细菌和差异菌属变化,评估差异菌属对CRF的诊断价值及其与肾功能的相关性。方法收集2017年8月至2018年1月来自山西省人民医院肾内科的56例CRF患者(CRF组)和健康体检中心38例健康对照者的粪便标本。用高通量测序技术分析肠道细菌16S rDNA V3-V4高变区序列,对CRF患者和健康体检者的肠道细菌进行α、β多样性分析、物种组成分析、差异物种分析。用受试者工作特征曲线(ROC)分析肠道差异菌属对CRF的诊断价值;Pearson相关分析差异菌属与估算肾小球滤过率(eGFR)的相关性。结果与健康对照组比较,CRF组患者粪便的α多样性降低(P﹤0.05),两组间β多样性存在结构差异(P﹤0.050)。在菌门水平上,CRF组中疣微菌门(Verrucomicrobia)的丰度较健康对照组显著降低(0.70%比3.09%,P﹤0.001)。CRF组放线菌门(Actinobacteria)的丰度较健康对照组显著升高(1.48%比1.14%,P=0.036)。属水平上,CRF组患者粪便中艾克曼菌(Akkermansia)(0.96%比3.90%)、副翅菌属(Parasutterella)(0.47%比0.93%)、乳酸菌属(Lactobacillus)(0.07%比0.48%)的丰度较健康对照组显著降低(均P﹤0.010);拟普雷沃菌属(Alloprevotella)(0.41%比0.04%)、梭菌属IV (Clostridium IV)(0.6%比0.1%)的丰度较健康对照组显著升高(均P﹤0.050)。ROC结果显示,差异菌属艾克曼菌(Akkermansia)诊断CRF的曲线下面积(AUC)为0.753,乳酸菌属(Lactobacillus)诊断CRF的AUC为0.792,两者联合检测诊断CRF的AUC为0.830,有较高的疾病诊断价值。Pearson相关分析结果提示,Lactobacillus丰度与eGFR水平呈显著正相关(R=0.29,P=0.029)。结论 CRF患者的肠道细菌的多样性和结构都发生了变化。差异菌属Akkermansia和Lactobacillus对CRF有一定的疾病诊断价值。Lactobacillus菌属丰度与eGFR呈正相关。

Objective To investigate changes in intestinal bacteria in chronic renal failure (CRF), their diagnostic value for CRF, and correlations between specific bacterial genera and renal function. Methods Fecal specimens were collected from 56 patients with CRF and 38 healthy controls in the Nephrology Department and Medical Examination Center of Shanxi People's Hospital between August 2017 and January 2018. High-throughput sequencing analysis of 16S rDNA V3-V4 hypervariable regions was performed for intestinal bacteria. Intestinal bacteria in CRF patients and healthy subjects were analyzed for alpha, beta diversity, species composition analysis, and differential species analysis. The diagnostic value of the presence of specific intestinal bacteria for CRF was analyzed using a receiver operating characteristic curve (ROC). Pearson's correlation analysis was used to analyze the correlation between the presence of specific genera and the estimated glomerular filtration rate (eGFR). Results The alpha and beta diversity in the CRF group was different from that in the control group (P﹤0.05). At the phylum level, Verrucomicrobia were significantly less abundant in the CRF group than that in the control group (0.70% vs 3.09%, P﹤0.001). The abundance of Actinobacteria was significantly greater in the CRF group than that in the control group (1.48% vs 1.14%, P=0.036). At the genus level, the abundance of Akkermansia (0.96% vs 3.90%), Parasutterella (0.47% vs 0.93%), and Lactobacillus (0.07% vs 0.48%) in the CRF group was significantly less than those in the control group (all P﹤0.01). The abundance of Alloprevotella (0.41% vs 0.04%) and Clostridium IV (0.6% vs 0.1%) was significantly greater than those in the control group (all P﹤0.05). The diagnostic value of CRF for the area under the ROC curve (AUC) for Akkermansia was 0.753, and that for Lactobacillus diagnostic value of CRF was 0.792. The combined AUC diagnostic value of CRF for detection of Akkermansia and Lactobacillus was 0.830, with high disease prediction value. Lactobacillus abundance was positively correlated with eGFR (R=0.29, P=0.029). Conclusions The diversity and structure of intestinal bacteria are altered in patients with CRF. The abundance of Akkermansia and Lactobacillus has diagnostic value for CRF. The abundance of Lactobacillus is positively correlated with eGFR.