Background/Purpose: Systemic lupus erythematosus (SLE) is the archetypic systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models in other inflammatory and autoimmune diseases have provided ample evidence of a role for intestinal bacteria in development of the systemic immune responses and autoreactivity, and on the resolution of inflammation and tissue injury.

Methods: To characterize the intestinal microbiome from cross-sectional surveys of an urban SLE patient cohort, we performed community profiling of 16S bacterial rRNA genes using next generation sequencing of 83 stool samples from well-characterized SLE adult patients and 16 healthy controls. Fecal samples were also fractionated for endogenous IgA coated bacteria vs. non-coated bacteria in 28 SLE and all healthy controls.

Results: Based on principal coordinates analysis of genomic bacterial extracts, SLE samples were significantly different in microbial composition from the healthy subjects (p<0.002). SLE subjects also demonstrated significantly greater intragroup diversity, yet there was an overlap with the healthy subjects. In terms of the species diversity, as measured by Chao1 alpha diversity metric, SLE microbiomes exhibited less diversity than healthy subjects (P<0.005). Similar patterns were observed based on Shannon diversity (P<0.01). In SLE, these patterns were seen in both treated patients and in those not taking medications. At a Phylum level, SLE patients displayed a significant increase in Proteobacteria and decrease in Firmicutes compared to controls. In addition, SLE patients had increased representation of specific operational taxonomic units (OTUs). Interestingly the anaerobic species Prevotella copri, recently linked to new-onset RA, was expanded in a subset of SLE patients but not in healthy controls. Studies of sorted IgA-coated bacteria also identified differential representation of certain OTU in SLE, which did not appear to be treatment related.

Conclusion: These studies provide the first demonstration that clinical SLE disease is associated with microbiome imbalances, with decreases in taxonomic diversity and blooms of specific OTU, within the intestine. Studies of the intestinal bacteria coated with IgA highlighted that only microbes of certain genera and OTU are immunologically recognized by the lupus host. We speculate that these candidate pathobiont species may act as triggers for disease initiation and flares.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-dysbiosis-within-the-intestinal-microbiome-contribute-to-sle-pathogenesis/