Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Department of Legal Medicine, Kansai Medical University, Osaka, Japan.
Am J Nephrol. 2018;47(3):164-170. doi: 10.1159/000487557. Epub 2018 Mar 13.
While the etiology of idiopathic nephrotic syndrome (idiopathic nephrotic syndrome [INS]; characterized by repeated relapses and comorbid allergic conditions) remains unknown, recent evidence suggests that dysfunction in regulatory T cells (Tregs) plays an important role in the development of INS as well as allergic diseases. We hypothesized that dysbiosis involving decreased butyric acid-producing gut microbiota leads to defective induction and differentiation of peripherally induced Tregs, resulting in INS relapse.
Study subjects were 12 children with INS, 8 classified as relapsing (R group; median age: 3.0 years) and 4 as non-relapsing (NR group; median age: 4.3 years), and 11 healthy children (HC group; median age: 5.1 years) serving as normal controls. Measurement of microbiota was performed using 16S ribosomal RNA metagenomic analysis, and fecal butyric acid was measured using high performance liquid chromatography. Flow-cytometric analysis of Tregs and CD4-positive (CD4+) cells in peripheral blood was also performed.
Metagenomic analysis of gut microbiota using feces showed that the proportion of butyric acid-producing bacteria was significantly lower in R (median 6.36%) than HC (median 18.84%; p = 0.0013), but no different between NR (median 16.71%) and HC (p = 0.29). Fecal organic acid analysis revealed significantly lower butyric acid quantities in R than HC (medians: 0.48 vs. 0.99 mg/g, p = 0.042). Circulating Tregs as a proportion of CD4+ cells were decreased in 75% of R and NR.
Pediatric relapsing INS patients show gut microbiota dysbiosis, characterized by a decreased proportion of butyric acid-producing bacteria and lower fecal butyric acid quantities, concomitant with reduced circulatory Tregs.
特发性肾病综合征（特发性肾病综合征 [INS]；以反复复发和合并过敏病为特征）的病因仍然未知，最近的证据表明，调节性 T 细胞（Tregs）功能障碍在 INS 以及过敏疾病的发展中起着重要作用。我们假设涉及产丁酸肠道微生物群减少的失调导致外周诱导的 Tregs的诱导和分化缺陷，导致 INS 复发。
研究对象为 12 名特发性肾病综合征患儿，8 名复发患儿（R 组；中位年龄：3.0 岁）和 4 名非复发患儿（NR 组；中位年龄：4.3 岁），以及 11 名健康儿童（HC 组；中位年龄：5.1 岁）作为正常对照。使用 16S 核糖体 RNA 宏基因组分析测量微生物群，使用高效液相色谱法测量粪便丁酸。还进行了外周血 Tregs 和 CD4 阳性（CD4+）细胞的流式细胞术分析。
粪便肠道微生物群的宏基因组分析显示，R 组（中位数 6.36%）丁酸产生菌的比例明显低于 HC 组（中位数 18.84%；p = 0.0013），但 NR 组（中位数 16.71%）与 HC 组无差异（p = 0.29）。粪便有机酸分析显示 R 组丁酸含量明显低于 HC 组（中位数：0.48 与 0.99 mg/g，p = 0.042）。75%的 R 和 NR 患儿循环 Tregs 占 CD4+细胞的比例下降。
儿科复发 INS 患者存在肠道微生物群失调，表现为产丁酸细菌比例降低和粪便丁酸含量降低，同时循环 Tregs 减少。
