Cheng Siyun, Chu Xiaojie, Wang Zhongyu, Khan Adeel, Tao Yue, Shen Han, Yang Ping
Department of Clinical Laboratory, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, 210008, China.
Department of Biotechnology, University of Science and Technology, Bannu, KP, Pakistan.
BMC Microbiol. 2025 May 7;25(1):275. doi: 10.1186/s12866-025-03995-5.
This study aims to explore the relationship between gut microbiota and fecal metabolomic profiles in patients with systemic lupus erythematosus (SLE), with and without lupus nephritis (LN), in order to identify potentially relevant biomarkers and better understand their association with disease progression.
Fecal samples from 15 healthy controls (HC) and 36 SLE patients (18 SLE-nonLN and 18 SLE-LN) were analyzed using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified using Linear Discriminant Analysis Effect Size (LEfSe) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Receiver Operating Characteristic (ROC) curve analyses were used to assess the potential clinical relevance of selected metabolites.
Beta diversity analysis demonstrated distinct microbial clustering between groups (p < 0.05). SLE-LN samples showed an increased relative abundance of Proteobacteria and decreased Firmicutes compared to SLE-nonLN. Metabolomic profiling identified multiple differentially abundant metabolites, with notable enrichment in primary bile acid biosynthesis pathways (e.g., Glycocholic acid, AUC = 0.951). In the SLE-nonLN group, increased Glycoursodeoxycholic acid levels (AUC = 0.922) were observed in pathways related to taurine and hypotaurine metabolism. Correlation analysis indicated a negative association between Escherichia-Shigella and bile acid levels (p < 0.01).
This integrative analysis suggests that patients with SLE and LN harbor distinct gut microbiota and metabolomic profiles. The identified microbial taxa and metabolites may have potential as non-invasive biomarkers and could contribute to a better understanding of SLE pathogenesis and progression.
本研究旨在探讨系统性红斑狼疮（SLE）患者（有或无狼疮性肾炎（LN））的肠道微生物群与粪便代谢组学特征之间的关系，以识别潜在的相关生物标志物，并更好地理解它们与疾病进展的关联。
使用16S rRNA基因测序和非靶向代谢组学分析了15名健康对照（HC）和36名SLE患者（18名非LN的SLE患者和18名LN的SLE患者）的粪便样本。使用线性判别分析效应大小（LEfSe）和正交偏最小二乘判别分析（OPLS-DA）鉴定差异微生物分类群和代谢物。使用京都基因与基因组百科全书（KEGG）通路和受试者工作特征（ROC）曲线分析来评估所选代谢物的潜在临床相关性。
β多样性分析表明各组之间存在明显的微生物聚类（p < 0.05）。与非LN的SLE相比，LN的SLE样本中变形菌门的相对丰度增加，厚壁菌门减少。代谢组学分析确定了多种差异丰富的代谢物，在初级胆汁酸生物合成途径中显著富集（例如，甘氨胆酸，AUC = 0.951）。在非LN的SLE组中，在与牛磺酸和低牛磺酸代谢相关的途径中观察到甘氨熊去氧胆酸水平升高（AUC = 0.922）。相关性分析表明大肠杆菌-志贺氏菌属与胆汁酸水平之间存在负相关（p < 0.01）。
这项综合分析表明，SLE和LN患者具有独特的肠道微生物群和代谢组学特征。所鉴定的微生物分类群和代谢物可能具有作为非侵入性生物标志物的潜力，并有助于更好地理解SLE的发病机制和进展。
