Correlation Between Gut Microbiota And Systemic Lupus Erythematosus And The Role Of Gut Klebsiella Pneumoniae In The Pathogenesis Of Hypertension

Objectives:Systemic lupus erythematosus(SLE)is a chronic systemic autoimmune disease whose onset and progression are affected by genetic and environmental factors.An increased titer of anti-dsDNA antibodies is generally regarded as highly specific and diagnostic for SLE.The exact etiology and pathogenic mechanism of SLE remains elusive,but genetic and environmental factors seem to play important roles.As one of the environmental factors,the role of gut microbiota in the pathogenesis of SLE remains unclear.The main purpose of this study is to clarify the role of gut microbiota in the pathogenesis of SLE and to investigate the pathophysiological mechanism,so as to provide theoretical basis for SLE pathogenesis research and disease treatment.Methods:Human fecal samples were collected from SLE patients and healthy control,and the mice fecal samples were collected from a lupus murine model and healthy mice.The composition and abundance of microbiota in these samples were examined using 16s rDNA sequencing.Germ free mice were given fecal microbiota transplantation(FMT),their microbiome were analyzed by sequencing.The serum level of autoantibodies specific for disease were determined using an ELISA.The immune cell profiles in mucosal immunity and peripheral immunity were analyzed by flow cytometry.Metagenomics,serum metabolomics and Phenotype MicroArrays of lupus microbiota were used to analyse different metabolism pathways.Gene expression with function analysis in receipts were examined by transcriptome sequencing and the expression of genes associated with SLE were determined using quantitative real-time PCR(qRT-PCR).Results:The fecal microbiota of SLE patients and SLE mice had different community richness and diversity compared with their healthy control.After FMT,microbiota of receipts was similar to their donors.Receipts of FMT from SLE patients or SLE mice also led to significant difference in the immune response and a significant increase in the titer of anti-dsDNA antibodies.Flow cytometry results indicated that FMT from SLE patients or SLE mice led to significant changes in the distribution of immune cells both in mucosal immunity and peripheral immunity organ.Metagenomic analysis indicated that carbohydrate and amino acid transport and metabolism were significantly different in lupus microbiota.Metabonomics and Phenotype MicroArrays analysis showed that histidine metabolism was significantly different.Transcriptome results indicated that different expression genes were mainly enriched in response to type I interferon and metabolism pathways.qRT-PCR identified expression of certain lupus susceptibility genes were upregulated.Conclusions:Microbiota participate in the pathogenesis of SLE.Microbiota from SLE transplanted into germ free mice increases titers of autoimmune antibodies specific for disease,their inflammation immune response,and expression of SLE susceptibility genes.Metabolic pathways were involved in differential expression.Gut microbiota can promote the pathogenesis of SLE.