ObjectivesSystemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.MethodsFecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients’ colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).ResultsThe fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.ConclusionsSLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

中文翻译：

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肠道菌群促进系统性红斑狼疮发病机制中的炎症反应

目的系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其发病和进展受遗传和环境因素影响。本研究的目的是确定肠道菌群在SLE发病机制中的影响，并探讨其相关机制。方法采用二代测序（NGS）对C57/BL6小鼠和SLE易感小鼠的粪便菌群进行检测。对无菌小鼠进行粪便微生物群移植 (FMT)，并通过 NGS 检查其肠道微生物组和受体结肠中的基因表达。使用酶联免疫吸附测定 (ELISA) 测定受者体内的抗双链 DNA (抗 dsDNA) 抗体。FMT后第3周通过流式细胞术分析小鼠的免疫细胞谱，并采用实时定量PCR（qRT-PCR）测定FMT后与SLE相关基因的表达量。结果SLE小鼠粪便微生物群较低群落丰富度和多样性高于健康小鼠。受体小鼠的粪便微生物群与其供体小鼠相似。SLE 小鼠的粪便微生物组可能导致抗 dsDNA 抗体显着增加，并促进受体小鼠的免疫反应。我们的结果还表明，SLE 小鼠的粪便微生物组导致免疫细胞分布发生显着变化，并上调某些狼疮易感基因的表达。结论 SLE 与肠道微生物群的改变有关。SLE 小鼠的粪便微生物组可以诱导无菌小鼠产生抗 dsDNA 抗体，刺激炎症反应，并改变这些小鼠 SLE 易感基因的表达。