Abstract
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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects connective tissues and is characterized by the presence of serum anti doublestranded DNA (Anti-dsDNA) antibodies (Rahman and Isenberg 2008)
SLE mice have reduced richness and abundance of fecal microbiota We first assessed the establishment of diseased model of SLE by measuring serum anti-dsDNA antibody titers, a defining characteristic of SLE
The results show that B6.NZM-Sle1NZM2410/AegSle2NZM2410/AegSle3NZM2410/Aeg/LmoJ congenic mouse (TC) (SLE) mice had significantly greater levels of antidsDNA antibodies than C57/B6 mice (Fig. 1a)
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects connective tissues and is characterized by the presence of serum anti doublestranded DNA (Anti-dsDNA) antibodies (Rahman and Isenberg 2008). An increased titer of anti-dsDNA antibodies is generally regarded as a specific diagnostic marker for human SLE (Mummert et al 2018), not all patients have high titers of anti-dsDNA antibodies (Sinico et al 2002). In lupus-prone mice, a high titer of anti-dsDNA antibodies is a specific marker for lupus, and some studies showed that a high titer of anti-dsDNA antibodies correlated with the severity of nephritis (Shen et al 1998; Blatt and Glick 1999; Niu et al 2008; Niu et al 2013). Many studies demonstrated that alterations of gut microbiota correlate with a variety of diseases, including autoimmune disorders such as SLE (Ma et al 2015; Liu et al 2019; Shi et al 2019)
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