Gut dysbiosis in a murine model of cutaneous lupus erythematosus correlates with antigen-specific T cells and antigen-presenting cells in skin

Abstract The commensal organisms constituting the human microbiome are increasingly appreciated to fortify epithelial barriers and modulate host immunity. Dysbiosis of both single strains and communities can contribute to inflammatory conditions. Here, we sought to characterize potential dysbiosis in our inducible mouse model of cutaneous lupus erythematosus (CLE). We hypothesized that gut dysbiosis would occur based on several studies that found lower Firmicutes/Bacteroidetes (F/B) ratios and decreased diversity in systemic lupus erythematosus (SLE) cohorts compared to healthy counterparts, a mouse study that identified Ro60 commensal orthologs that can trigger onset of lupus-like disease, and a study of CLE that identified outgrowth of Staphylococcus aureus in the skin. Using whole genome shotgun sequencing, we identified differences in pre- and post-irradiation cohorts, particularly an increase in Duncaniella , a decrease in Prevotella , and a reduction in alpha diversity following irradiation. Baseline alterations in CLE mice gut bacteria compared to littermate controls were also extant, including trends toward increased Parabacterides distasonis and Bacteroides acidifaciens in CLE mice. Importantly, we noted an increase in Phocaeicola sartorii in CLE mice compared to littermate controls post-disease induction. We examined the mycobiome in our mice and noted a reduction of Colletotrichum tofieldiae specifically in CLE mice post-disease induction, and a trend towards increased Periglandula ipomoeae . Last, we correlated abundance of genera and species with flow cytometry data obtained from the skin, lymph node and spleen, and identified specific strains that correlated with presence of antigen-specific T cells and different antigen presenting cell populations. Thus, our model exhibits similar changes to other models of lupus-like disease, and our data identify potential novel strains/species that could be modified for CLE and/or SLE treatment such as through generation of probiotics or specific antimicrobial agents.