Ali Aya Y, Zahran Sara A, Eissa Mervat, Kashef Mona T, Ali Amal Emad
Microbiology & Immunology Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 12311, Egypt.
Rheumatology & Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.
Gut Pathog. 2025 Feb 18;17(1):10. doi: 10.1186/s13099-025-00683-7.
Gut microbial dysbiosis and leaky gut play a role in systemic lupus erythematosus (SLE). Geographical location and dietary habits affect the microbiome composition in diverse populations. This study explored the gut microbiome dysbiosis, leaky gut, and systemic immune response to gut bacterial consortium in patients with SLE exhibiting mild/moderate and severe disease activity.
Fecal and blood samples were collected from patients with SLE and healthy volunteers. Genomic DNA was extracted from the stool samples and subjected to 16S rRNA amplicon sequencing and microbiome profiling. Additionally, enzyme-linked immunosorbent assays were employed to determine the serum lipopolysaccharide level, as an assessment of gut permeability, and the systemic immune response against gut bacteria.
Patients with SLE showed significantly lower gut bacterial richness and diversity, indicated by observed OTUs (56.6 vs. 74.44; p = 0.0289), Shannon (3.05 vs. 3.45; p = 0.017) and Simpson indices (0.91 vs. 0.94; p = 0.033). A lower Firmicutes-to-Bacteroidetes ratio (1.07 vs. 1.69; p = 0.01) was observed, with reduced genera such as Ruminococcus 2 (0.003 vs. 0.026; p = 0.0009) and Agathobacter (0.003 vs. 0.012; p < 0.0001) and elevated Escherichia-Shigella (0.04 vs. 0.006; p < 0.0001) and Bacteroides (0.206 vs. 0.094; p = 0.033). Disease severity was associated with a higher relative abundance of Prevotella (0.001 vs. 0.0001; p = 0.04). Medication effects included lower Romboutsia (0.0009 vs. 0.011; p = 0.005) with azathioprine and higher Prevotella (0.003 vs. 0.0002; p = 0.038) with cyclophosphamide. Furthermore, categorization by prednisolone dosage revealed significantly higher relative abundances of Slackia (0.0007 vs. 0.00002; p = 0.0088), Romboutsia (0.009 vs. 0.002; p = 0.0366), and Comamonas (0.002 vs. 0.00007; p = 0.0249) in patients receiving high-dose prednisolone (> 10 mg/day). No differences in serum lipopolysaccharide levels were found, but SLE patients exhibited elevated serum gut bacterial antibody levels, suggesting a systemic immune response.
This study confirms the gut microbiome dysbiosis in patients with SLE, influenced by disease severity and specific medication usage.
肠道微生物失调和肠屏障功能障碍在系统性红斑狼疮（SLE）中起作用。地理位置和饮食习惯会影响不同人群的微生物组组成。本研究探讨了疾病活动度为轻度/中度和重度的SLE患者的肠道微生物失调、肠屏障功能障碍以及对肠道细菌群落的全身免疫反应。
收集SLE患者和健康志愿者的粪便和血液样本。从粪便样本中提取基因组DNA，并进行16S rRNA扩增子测序和微生物组分析。此外，采用酶联免疫吸附测定法测定血清脂多糖水平，以评估肠道通透性，并检测针对肠道细菌的全身免疫反应。
SLE患者的肠道细菌丰富度和多样性显著降低，表现为观察到的操作分类单元（OTUs）数量减少（56.6对74.44；p = 0.0289）、香农指数降低（3.05对3.45；p = 0.017）和辛普森指数降低（0.91对0.94；p = 0.033）。观察到厚壁菌门与拟杆菌门的比例降低（1.07对1.69；p = 0.01），瘤胃球菌2属（0.003对0.026；p = 0.0009）和阿加托杆菌属（0.003对0.012；p < 0.0001）等属减少，而大肠杆菌-志贺氏菌属（0.04对0.006；p < 0.0001）和拟杆菌属（0.206对0.094；p = 0.033）增加。疾病严重程度与普雷沃氏菌属的相对丰度较高有关（0.001对0.0001；p = 0.04）。药物影响包括使用硫唑嘌呤时罗姆布茨菌属降低（0.0009对0.011；p = 0.005），使用环磷酰胺时普雷沃氏菌属增加（0.003对0.0002；p = 0.038）。此外，根据泼尼松龙剂量分类显示，接受高剂量泼尼松龙（>10mg/天）的患者中，斯拉基菌属（0.0007对0.00002；p = 0.0088）、罗姆布茨菌属（0.009对0.002；p = 0.0366）和丛毛单胞菌属（0.002对0.00007；p = 0.0249）的相对丰度显著更高。血清脂多糖水平未发现差异，但SLE患者的血清肠道细菌抗体水平升高，提示存在全身免疫反应。
本研究证实了SLE患者存在肠道微生物失调，且受疾病严重程度和特定药物使用的影响。
