Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Pediatr Int. 2021 Sep;63(9):1011-1019. doi: 10.1111/ped.14679. Epub 2021 Aug 5.
Childhood nephrotic syndrome is idiopathic in 90% of cases. Despite its relatively high prevalence (30-35 per 100 000 individuals under 15 years old), the etiology of the disease remains elusive. It has become clear that oxidants are elevated, and antioxidants are decreased, at onset of idiopathic nephrotic syndrome (INS). It was suggested that overexpression of podocyte CD80 induced by abnormalities of Tregs was involved in the pathogenesis of INS. Subsequently, it became clear that quantitative or qualitative reduction of Tregs has a profound impact on the development of INS. To address why Tregs are decreased at onset of INS, it was hypothesized that a decrease in Tregs may be associated with dysbiosis. Given the critical role of butyrate-producing bacteria in the differentiation of Tregs, the gut microbiota was analyzed with a particular focus on the abundance of butyrate-producing bacteria, and it was found that pediatric patients with INS had low levels of butyrate in their stool and a low percentage of butyrate-producing bacteria. Interestingly, it was recently reported that gut dysbiosis increases oxidative stress in the intestinal tract. Taken together, we currently hypothesize that gut dysbiosis is associated with a predisposition to INS because of immunological abnormalities characterized by abnormal Tregs with increased oxidative stress.
儿童肾病综合征有 90%的病例为特发性。尽管其发病率相对较高（每 10 万名 15 岁以下个体中有 30-35 例），但病因仍难以捉摸。目前已经清楚，特发性肾病综合征（INS）发病时氧化应激升高，抗氧化剂减少。有研究表明，Treg 异常导致足细胞 CD80 过表达，参与了 INS 的发病机制。随后，人们清楚地认识到 Treg 的数量或质量减少对 INS 的发展有深远影响。为了解释为什么 INS 发病时 Treg 减少，有人假设 Treg 减少可能与肠道菌群失调有关。鉴于丁酸产生菌在 Treg 分化中的关键作用，对肠道微生物组进行了分析，特别关注丁酸产生菌的丰度，结果发现 INS 患儿粪便中丁酸水平较低，丁酸产生菌的比例也较低。有趣的是，最近有报道称，肠道菌群失调会增加肠道的氧化应激。综上所述，我们目前假设肠道菌群失调与 INS 的易感性有关，因为免疫异常表现为 Treg 异常，伴有氧化应激增加。
