益生菌干预治疗狼疮肾炎Ⅳ~Ⅴ型患者的效果研究

Effect of Probiotic Intervention on ClassⅣandⅤLupus Nephritis

背景益生菌辅助狼疮肾炎(LN)患者治疗可显著提高治疗效果,但缺乏药物疗效之间的比较以及益生菌干预治疗对患者肠道菌群影响的研究。目的观察益生菌干预治疗LN的疗效及对肠道菌群的影响。方法选择2019—2020年在湘南学院附属医院肾内科诊断为Ⅳ型和Ⅴ型LN患者98例,采用隐匿数字随机法将患者分为常规治疗组和干预治疗组。常规治疗组给予常规治疗,干预治疗组同时给予益生菌干预治疗,两组均治疗24周,比较两组患者的临床疗效,包括24 h尿蛋白定量、尿素氮(BUN)、血肌酐(Scr)、血清免疫球蛋白(Ig)E、IgG水平、血清炎性因子水平以及粪便肠道菌群变化、粪便中短链脂肪酸水平等。结果共93例患者完成了24周的治疗,其中常规治疗组46例,干预治疗组47例。两组患者性别、年龄、体质指数(BMI)及治疗前收缩压、舒张压、血红蛋白、血清白蛋白、Scr、补体C3和补体C4比较,差异均无统计学意义(P>0.05)。治疗24周后,干预治疗组系统性红斑狼疮肾脏疾病活动指数(R-SLEDAI)评分低于常规治疗组(P<0.05)。治疗4、12、24周后,两组患者24 h尿蛋白定量、BUN、Scr较治疗前降低(P<0.05);且治疗24周后,干预治疗组患者24 h尿蛋白定量和BUN均低于常规治疗组(P<0.05)。治疗24周后,两组患者血清IgE、IgG水平均较治疗前下降,且干预治疗组患者血清IgE、IgG水平低于常规治疗组(P<0.05)。治疗24周后,两组患者C反应蛋白(CRP)、白介素(IL)-6、肿瘤坏死因子(TNF)-α水平均较治疗前下降,且干预治疗组患者CRP、IL-6、TNF-α水平低于常规治疗组(P<0.05)。LEfSe分析显示,LN患者治疗前粪便中幽门螺杆菌属、梭状芽孢杆菌、肠球菌门等有害菌群明显增加,疣微菌门等有益菌群含量明显降低。常规治疗组治疗24周后粪便中幽门螺杆菌属、梭状芽孢杆菌、肠球菌门降低,疣微菌门等有益菌群明显增加,且干预治疗组治疗24周后疗效更加明显。常规治疗组治疗24周后和干预治疗组治疗后粪便中乙酸、丙酸、丁酸含量均较治疗前明显增加,且干预治疗组治疗24周后粪便中乙酸、丙酸、丁酸含量较常规治疗组治疗后明显增加(P<0.05)。结论益生菌干预治疗LN可以增加阿克曼菌丰度,提高粪便中乙酸、丙酸、丁酸含量,降低血清Ig水平,改善肾脏功能。

Background As an adjuvant therapy,probiotics can significantly improve the therapeutic effect in lupus nephritis.But there is a lack of comparative studies of efficacies of drug treatments and effects of probiotics on gut flora.Objective To observe the therapeutic efficacy,and gut flora changes induced by probiotics as an adjuvant therapy for lupus nephritis.Methods Ninety-eight patients with classⅣandⅤlupus nephritis were selected from Department of Nephrology,Affiliated Hospital of Xiangnan University from 2019 to 2020,and randomized into a routine group(routine treatment)and an intervention group(routine treatment plus probiotics)under allocation concealment.Intergroup comparison of clinical efficacies was conducted after 24-week treatment in terms of levels of 24-hour urine protein,blood urea nitrogen,serum creatinine,serum IgE,IgG,and serum inflammatory markers,as well as fecal flora changes and fecal short-chain fatty acid concentrations.Results A total of 93 cases(46 in routine group,and 47 in intervention group)who completed the therapeutic follow-up were included for final analysis.Both groups had no statistically significant differences in sex ratio,mean age,BMI,baseline levels of systolic blood pressure,diastolic blood pressure,hemoglobin,serum albumin,serum creatinine,complement C3 and complement C4(P>0.05).At the end of treatment,the intervention group demonstrated lower mean Systemic Lupus Erythematosus Disease Activity Indexof Renal(P<0.05).The 24-hour urinary protein,blood urea nitrogen and serum creatinine decreased notably in both groups at the end of 4,12 and 24 weeks of treatment(P<0.05),and the 24-hour urinary protein and blood urea nitrogen in intervention group at the end of 24-week treatment were even more lower(P<0.05).When the 24-week treatment ended,serum IgE and IgG levels decreased notably in both groups(P<0.05),and they deceased even more significantly in intervention group(P<0.05).Moreover,serum C-reactive protein,IL-6 and TNF-αdecreased significantly in both groups(P<0.05),and they deceased even more significantly in the intervention group(P<0.05).Linear discriminant analysis effect size analysis indicated that at baseline,harmful gut flora such as Helicobacter pylori,Clostridium,and Enterococcus,significantly increased while Verrucomicrobia and other beneficial gut flora significantly decreased in all participants.After the 24-week treatment,the above-mentioned harmful gut flora decreased and beneficial gut flora increased in all participants,and such changes were more significant in the intervention group.Fecal acetic acid,propionic acid,and butyric acid increased significantly in all participants compared to the baseline levels,and they increased even more significantly in the intervention group(P<0.05).Conclusion Adjuvant treatment of lupus nephritis with probiotics could promote the recovery of renal function,by elevating the abundance of Akkermansiaceae,contents of fecal acetic acid,propionic acid,and butyric acid,and lowering serum immunoglobulin.