Systemic lupus erythematosus (SLE) is linked to host gut dysbiosis. Here we performed faecal gut microbiome sequencing to investigate SLE-pathogenic gut microbes and their potential mechanisms. There were 134 healthy controls (HCs) and 114 SLE cases for 16 S ribosomal RNA (rRNA) sequencing and 97 HCs and 124 SLE cases for shotgun metagenomics. Faecal microbial changes and associations with clinical phenotypes were evaluated, and SLE-associated microbial genera were identified in amplicon analysis. Next, metagenomic sequencing was applied for accurate identification of microbial species and discovery of their metabolic pathways and immunogenic peptides both relevant to SLE. Finally, contribution of specific taxa to disease development was confirmed by oral gavage into lupus-prone MRL/lpr mice. SLE patients had gut microbiota richness reduction and composition alteration, particularly lupus nephritis and active patients. Proteobacteria/Bacteroidetes (P/B) ratio was remarkably up-regulated, and Escherichia was identified as the dominantly expanded genus in SLE, followed by metagenomics accurately located Escherichia coli and Escherichia unclassified species. Significant associations primarily appeared among Escherichia coli, metabolic pathways of purine nucleotide salvage or peptidoglycan maturation and SLE disease activity index (SLEDAI), and between multiple epitopes from Escherichia coli and disease activity or renal involvement phenotype. Finally, gavage with faecal Escherichia revealed that it upregulated lupus-associated serum traits and aggravated glomerular lesions in MRL/lpr mice. We characterize a novel SLE exacerbating Escherichia outgrowth and suggest its contribution to SLE procession may be partially associated with metabolite changes and cross-reactivity of gut microbiota-associated epitopes and host autoantigens. The findings could provide a deeper insight into gut Escherichia in the procession of SLE.

中文翻译：

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埃希菌的生长易加重系统性红斑狼疮


系统性红斑狼疮 （SLE） 与宿主肠道菌群失调有关。在这里，我们进行了粪便肠道微生物组测序，以研究 SLE 致病性肠道微生物及其潜在机制。16 S 核糖体 RNA （rRNA） 测序有 134 例健康对照 （HCs） 和 114 例 SLE，鸟枪法宏基因组学有 97 例 HCs 和 124 例 SLE。评价粪便微生物变化及其与临床表型的相关性，并在扩增子分析中鉴定出 SLE 相关微生物属。接下来，应用宏基因组测序准确鉴定微生物种类并发现其代谢途径和免疫原性肽，两者都与 SLE 相关。最后，通过对狼疮易感 MRL/lpr 小鼠进行口服强饲证实了特定分类群对疾病发展的贡献。SLE 患者肠道菌群丰富度降低和成分改变，尤其是狼疮性肾炎和活动期患者。变形菌门/拟杆菌门 （P/B） 比值显著上调，埃希菌属被确定为 SLE 中优势扩增的属，其次是宏基因组学准确定位大肠杆菌和未分类的埃希菌属。显著关联主要出现在大肠埃希菌、嘌呤核苷酸挽救或肽聚糖成熟代谢途径与 SLE 疾病活动指数 （SLEDAI） 之间，以及大肠埃希菌的多个表位与疾病活动或肾脏受累表型之间。最后，粪便大肠杆菌管饲法显示，它上调了狼疮相关血清性状并加重了 MRL/lpr 小鼠的肾小球病变。 我们描述了一种加剧埃希氏菌生长的新型 SLE，并表明其对 SLE 游行的贡献可能与肠道微生物群相关表位和宿主自身抗原的代谢物变化和交叉反应性部分相关。这些发现可以更深入地了解 SLE 过程中的肠道大肠杆菌。