human gut metagenome Metagenome. human gut metagenome

Systemic lupus erythematosus (SLE), characterized by chronic inflammation and multi-organ damage, has been suggested to associate with gut dysbiosis. To shed new light on the role of microbiota in SLE development, we analyzed the fecal metagenome of 117 treatment-naïve SLE patients with 52 post-treatment data and 115 sex- and age-matched healthy controls (HC) by deep-sequencing. Metagenomic profiling of MRL/lpr mice was also performed for discovering shared microbial signatures between lupus patients and mice. We found significant differences in microbial composition and function between SLE and HC, revealing multiple plausible contributing bacterial species and metabolic pathways. In-depth SNP-based analysis revealed an oral-microbiome origin for two marker species. Lastly, we confirmed experimentally that peptides of SLE-enriched species mimicking autoantigens such as Sm and Fas could trigger autoimmune responses. Taken together, our study deepened understanding of the disordered gut microbiota in SLE patients, part of which being a result of translocation from oral microbiota. We also discovered new microbial peptides which may be causal of SLE development via molecular mimicry.