狼疮性肾炎患者肠道菌群变化及代谢物硫酸吲哚酚分析

Analysis of Intestinal Flora and Indoxyl Sulfate in the Patients with Lupus Nephritis

摘要: 目的：分析狼疮性肾炎(Lupus nephritis, LN)患者与健康人群肠道菌群的结构及代谢产物差异，探讨肠道菌群在LN发病中的作用。方法：选取系统性红斑狼疮患者51例，分为狼疮性肾炎组(LN组) 27例和狼疮非肾炎组(N-LN组) 24例，另选取53例健康志愿者作为健康对照组(H组)。基于Illumina MiSeq平台分别对SLE患者和健康对照组的粪便样本进行Alpha多样性分析、Beta多样性分析以及属水平上的菌群差异性分析，采用ELISA双抗体夹心法测定SLE患者和健康对照组血清硫酸吲哚酚(IS)浓度，对LN患者的24h尿蛋白定量与其血清IS浓度进行Pearson相关性分析，采用受试者工作曲线(ROC曲线)，根据最佳敏感性和特异性确定IS诊断界点。结果：LN组较健康对照组血IS浓度和肠杆菌含量均显著升高，差异有统计学意义(P < 0.05)。在LN患者中，24 h尿蛋白定量与血清IS浓度呈正相关(r = 0.86, P < 0.01)。结论：狼疮性肾炎患者存在肠道菌群失调，肠杆菌含量明显增加，相关代谢产物血清IS异常，可能参与LN发病。

Abstract: Objective: To analyze the structure and metabolites of intestinal flora in patients with lupus nephritis and healthy controls, and to explore the role of intestinal flora in the pathogenesis of LN. Methods: 51 patients with systemic lupus erythematosus were divided into the lupus nephritis group (group LN, n = 27) and the lupus non-glomerulonephritis group (group N-LN, n = 24), and 53 healthy volunteers were selected as the healthy control group (group H). Based on the IlluminaMiSeq platform, the fecal samples of SLE patients and healthy controls were analyzed by Alpha diversity analysis, Beta diversity analysis and flora difference analysis at genus level. The blood Indoxyl sulfate (IS) concentration in SLE patients and healthy controls was determined by ELISA double antibody sandwich method. The correlation between the 24 h urinary protein quantification and the blood IS concentration in LN patients was examined by the Pearson correlation test. The best cutoffs for the blood IS concentration in predicting a 24 h urinary protein quantification were determined with the receiver operating characteristic curve (ROC). Results: The blood IS concentration and the content of fecal Faecalibacterium in group LN were significantly higher than those in the healthy control group (P < 0.05). In patients with LN, the 24 h urinary protein quantification was positively correlated with the blood IS concentration (r = 0.86, P < 0.01). Conclusion: The patients with lupus nephritis have intestinal flora imbalance, the content of fecal Faecalibacterium is significantly increased, and the blood IS concentration is abnormal, which may be involved in the pathogenesis of LN.