系统性红斑狼疮与肠道菌群的相关研究

Correlation between systemic lupus erythematosus and gut microbiota

目的探讨SLE与肠道菌群、炎症因子及疾病活动度之间的关系,以及经糖皮质激素(激素)联合羟氯喹治疗后三者的变化及其治疗作用机制。方法选择25名健康体检者(正常对照组)及30例初诊SLE患者(SLE组),后者接受为期3个月的激素联合羟氯喹治疗,分别收集正常对照组及SLE组患者治疗前后的粪便标本,应用SYBR Green I实时荧光定量PCR对大肠埃希菌、双歧杆菌、乳酸杆菌定量,同时应用ELISA法对外周血中IL-17、转化生长因子-β(TGF-β)的表达水平进行检测,并行SLE疾病活动指数(SLEDAI)评价SLE患者的病情活动程度。结果与正常对照组相比,治疗前SLE患者大肠埃希菌数较多(P<0.01),双歧杆菌、乳酸杆菌数较少(P均<0.01);外周血中IL-17水平较高(P<0.05),且与SLEDAI评分呈正相关(r=0.699,P<0.05);TGF-β水平下降(P<0.05),且与乳酸杆菌的数量呈正相关(r=0.416,P<0.05)。与治疗前相比,激素联合羟氯喹治疗3个月后SLE患者粪便中双歧杆菌、乳酸杆菌数减少(P均<0.05),大肠埃希菌数无明显变化(P>0.05);SLE患者SLEDAI评分降低(P<0.05),血清IL-17水平下降(P<0.01)、但仍高于正常对照组(P<0.01),TGF-β水平升高(P<0.01)、但仍低于正常对照组(P<0.05)。结论 SLE患者存在较明显的肠道菌群失调状态。激素联合羟氯喹治疗可改善SLE患者的病情,但同时可能会进一步加重肠道菌群失调状态。IL-17及TGF-β等炎症因子可能参与SLE的发病及治疗作用机制。SLE状态下,乳酸杆菌与TGF-β可能有关。

Objective To analyze the relationship among systemic lupus erythematosus （ SLE） ,gut microbiota, inflammatory cytokines and disease activity, and to explore the effect and potential mechanism of glucocorticoid combined with hydroxychloroquine therapy on their relationship. Methods Twenty five healthy individuals （ control group） and 30 patients with new-onset SLE （ SLE group） were recruited in this study. Patients in the SLE group received combined therapy of glucocorticoid and hydroxychloroquine for three months. Fecal samples were obtained before and after corresponding treatment in two groups. SYBR Green I real-time PCR was performed to measure the quantity of the Escherichia coli, Baeteroides and Lactobacillus. The expression levels of IL-17 and TGF-β in peripheral blood were detected by ELISA. The disease activity of SLE patients was evaluated by SLE disease activity index （SLEDAI）. Results Compared with the control group, the copies of Escherichia coli in SLE patients were significantly increased, whereas the quantity of Baeteroides and Lactobacillus was significantly decreased （ all P 〈 0. 01）. The level of serum IL-17 was significantly up-regulated （P 〈 0.05 ） , and positively correlated with SLEDAI score （ r=0. 699, P 〈 0.05 ） . The level of serum TGF-β was significantly down-regulated （P 〈0. 05） , and positively correlated with the copies of Lactobacillus （r = 0. 416, P 〈0.05 ）. After 3-month corticosteroid combined with hydroxychloroquine therapy, the quantity of Baeteroides and Lactobacillus was further reduced （ both P 〈 0. 05 ） , while no significant change was observed in the copies of Escherichia coli （ P 〉 0. 05 ） . In SLE patients, SLEDAI score was reduced （ P 〈 0. 05 ） and the level of serum IL-17 was down-regulated （P 〈 0 . 0 1 ） , still significantly higher than that in the control group （P 〈0. 01）. The level of serum TGF-β was up-regulated （P 〈0. 01） , still lower compared with that in the control group （ P 〈 0. 05 ）. Conclusions SLE patients present with evident state of intestinal dysbacteriosis. Combined therapy of glucocorticoid and hydroxychloroquine can significantly alleviate the severity of SLE, whereas may further aggravate the state of intestinal dysbacteriosis. The inflammatory cytokines of IL-17 and TGF-β may be involved in the pathogenesis and therapeutic mechanism of SLE. Lactobacillus is probably corre-lated with TGF-β in SLE patients.