Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified.

We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing.

Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria–Gammaproteobacteria–Enterobacteriales–Enterobacteriaceae–Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN.

Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

肠道菌群失调被认为参与了 IgA 肾病 (IgAN) 的发病机制。然而，与 IgAN 发病和治疗反应密切相关的关键细菌分类群尚未确定。

我们招募了 127 名未经治疗的 IgAN 患者和 127 名匹配的健康对照 (HC)，他们被随机分为发现队列和验证队列，以研究他们的肠道微生物群特征并建立 IgAN 的细菌诊断模型。对 56 名患者和 HC 的单独队列进行了调查，以评估跨区域验证。另外 40 名原发性膜性肾病 (MN) 患者被纳入研究，以探索疾病特异性验证。对 77 名患者的亚组进行了前瞻性随访，以进一步剖析免疫抑制治疗 6 个月后肠道菌群改变与治疗反应之间的关联。从所有参与者收集粪便微生物群样本，并使用 16S 核糖体 RNA 测序进行分析。

观察到α多样性降低（Shannon，P =0.03）、微生物组成改变（Adonis，P =0.0001），以及分类链变形菌门– γ-变形菌门–肠杆菌目–肠杆菌科–大肠杆菌-志贺氏菌的显着扩展（所有P <0.001）在未经治疗的 IgAN 患者中，仅在免疫抑制治疗 6 个月后达到临床缓解的患者中逆转。重要的是，七个可操作的分类单元，其中大肠杆菌-志贺氏菌贡献最大，被确定为 IgAN 的最佳细菌分类器（在发现、验证和跨区域验证集中的 AUC 分别为 0.8635、0.8551、0.8026），但不能有效地区分 IgAN 患者与 MN 患者（ AUC=0.6183）。细菌功能预测进一步验证了 IgAN 中志贺菌感染途径的富集。

肠道菌群失调以大肠杆菌-志贺氏菌属的显着扩张为特征，是 IgAN 患者的标志，可作为 IgAN 有前景的诊断生物标志物和治疗靶点。需要进一步的研究来调查大肠杆菌-志贺氏菌在 IgAN 发病机制中的潜在贡献。