Liang Xiaolin, Zhang Simeng, Zhang Difei, Hu Liang, Zhang La, Peng Yu, Xu Yuan, Hou Haijing, Zou Chuan, Liu Xusheng, Chen Yang, Lu Fuhua
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Front Mol Biosci. 2022 Aug 24;9:970723. doi: 10.3389/fmolb.2022.970723. eCollection 2022.
IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. and levels were higher, while and levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by was closely related to the IgAN patients. Moreover, , and were characteristic bacteria enriched in IgAN patients. Spearman's correlation analysis found that and were positively correlated with urine protein-creatinine ratio, while showed a direct association with red blood cells in urine, and and were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by were enriched in IgAN patients. These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.
IgA肾病（IgAN）是亚洲最常见的肾小球肾炎类型。其发病机制涉及半乳糖缺陷型IgA1（Gd-IgA1）表达升高和肠道黏膜免疫失调。本研究的目的是探讨特定肠道微生物群及相关酶是否影响IgAN中的Gd-IgA1。本研究对2016年1月至2018年12月在广州中医药大学第二临床医学院招募的20例IgA肾病患者（IgAN组）和20例健康对照者（HCs组）的粪便样本进行了Illumina鸟枪法宏基因组测序。进行肠道微生物群差异分析以确定总体微生物群组成、代表性肠型和微生物群丰度。通过Spearman分析评估肠道微生物群与临床指标之间的相关性。此外，分别使用MetaCyc途径和bioBakery三个平台对微生物群落进行功能预测和微生物组编码酶的定量计算。与HCs组相比，IgAN组的[具体指标1]和[具体指标2]水平较高，而[具体指标3]和[具体指标4]水平较低。以[具体细菌名称]为特征的肠型I与IgAN患者密切相关。此外，[具体细菌名称1]、[具体细菌名称2]和[具体细菌名称]是IgAN患者中富集特征性细菌。Spearman相关性分析发现，[具体细菌名称1]和[具体细菌名称2]与尿蛋白肌酐比值呈正相关，而[具体细菌名称3]与尿红细胞呈直接关联，[具体细菌名称4]和[具体细菌名称5]与估算肾小球滤过率（eGFR）呈正相关。这些结果表明IgAN患者存在肠道菌群失调，且与临床和生化特征相关。此外，MetaCyc途径分析预测微生物群相关代谢途径，包括氨基酸和聚糖的生物合成，与IgAN组相关。微生物酶分析强调，IgAN患者中富集了由[具体细菌名称]分泌的与Gd-IgA1相关的α-半乳糖苷酶和α-N-乙酰半乳糖胺酶。这些发现表明，由[具体细菌名称]分泌的α-半乳糖苷酶和α-N-乙酰半乳糖胺酶可能与Gd-IgA1的产生有关，表明源自异常肠道微生物群的酶可能有助于Gd-IgA1的产生，并在IgAN的发病机制中起重要作用。
