Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Med Hypotheses. 2017 Oct;108:35-37. doi: 10.1016/j.mehy.2017.07.035. Epub 2017 Aug 1.
Nephrotic syndrome characterized by heavy proteinuria and edema is the most common chronic kidney disease in children. It is classified into three categories, of which the idiopathic type accounts for the vast majority of cases. As indicated by the name, the etiology of idiopathic nephrotic syndrome remains unknown though it has been suggested that impaired T cell function is involved. Recently, evidence has mounted to suggest that dysfunction in regulatory T cells plays an important role in the development of allergic disease, a recognized comorbid condition for children with idiopathic nephrotic syndrome. It is known that regulatory T cells are mainly induced by short chain fatty acids produced by gut microbiota and that children with allergy are reported to have aberrant gut microbiota. On this basis, we hypothesize that an aberrant microbiota, i.e., dysbiosis in the gut resulting in defective induction of regulatory T cells, is also involved in the etiology of idiopathic nephrotic syndrome in children. Our hypothesis can be directly tested by metagenome analysis using bacterial DNA extracted from the feces of patients with idiopathic nephrotic syndrome. Indirect evidence could be obtained by epidemiological survey, such as a comparative study of the environmental factors influencing the initial colonization of gut microbiota between patients with idiopathic nephrotic syndrome and age-matched healthy children. Factors that may disrupt this colonization include a cesarean delivery, formula feeding, excessive use of antibiotics, or the introduction of inappropriate solid foods containing a high amount of saturated fat. Based on this hypothesis, we suggest it would be clinically worthwhile to study whether administration of probiotics composed of commensal bacteria known to efficiently induce regulatory T cells in vitro could control the exacerbation or relapse of INS.
肾病综合征的特征是大量蛋白尿和水肿，是儿童中最常见的慢性肾脏病。它分为三类，其中特发性占绝大多数。顾名思义，特发性肾病综合征的病因仍不清楚，但有研究表明，T 细胞功能受损与此有关。最近的证据表明，调节性 T 细胞功能障碍在过敏性疾病的发生中起着重要作用，而过敏性疾病是特发性肾病综合征儿童的一种公认的合并症。已知调节性 T 细胞主要由肠道微生物群产生的短链脂肪酸诱导，而过敏儿童的肠道微生物群存在异常。在此基础上，我们假设异常的微生物群，即肠道失调导致调节性 T 细胞的诱导缺陷，也与儿童特发性肾病综合征的病因有关。我们的假设可以通过使用从特发性肾病综合征患者粪便中提取的细菌 DNA 进行宏基因组分析直接进行测试。间接证据可以通过流行病学调查获得，例如对特发性肾病综合征患者和年龄匹配的健康儿童肠道微生物群初始定植影响因素的环境因素进行比较研究。可能破坏这种定植的因素包括剖宫产、配方奶喂养、过度使用抗生素或引入含有大量饱和脂肪的不合适的固体食物。基于这一假设，我们建议研究体外已知能有效诱导调节性 T 细胞的共生菌组成的益生菌是否能控制 INS 的恶化或复发，这在临床上是有价值的。
