Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 25; no. 1; pp. 35 - 16
• Main Authors: Ma, Yiyangzi, Xu, Xiaoxue, Li, Mengtao, Cai, Jun, Wei, Qiang, Niu, Haitao
• Format: Journal Article
• Language: English
• Published: England BioMed Central 01.08.2019; BMC
• Subjects: Antibodies; Discriminant analysis; Disease; Fecal microbiota transplantation2; Feces; Gene expression; Genomes; Gut microbiota; Gut microbiota1; Hypotheses; Immune response; Immune response4; Immune system; Laboratory animals; Lupus; Lupus susceptibility gene5; Medical research; Microbiota; Pathogenesis; Software; Systemic lupus erythematosus3; Taxonomy; United States > US; Fecal microbiota transplantation2; Immune response4; Gut microbiota1; Lupus susceptibility gene5; Systemic lupus erythematosus3
• ISSN: 1076-1551; 1528-3658; 1528-3658
• DOI: 10.1186/s10020-019-0102-5

Systemic 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. Fecal 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). The 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. SLE 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.