Characterizing the role of Lactobacillus spp. in systemic lupus erythematosus

Abstract

Abstract Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with no known cure. The role of gut microbiota and its interaction with the immune system can direct tolerance induction to self-antigens not only in the intestinal mucosa but also at the systemic level. Our lab previously showed differences between the gut microbiota in lupus-prone MRL/Mp-Faslpr (lpr) mice compared to healthy controls, with lower Lactobacillaceae levels in lpr mice. Restoring the microbiota with a mix of 5 different Lactobacillus strains, L. reuteri, L. oris, L. johnsonii, L. gasseri, and L. rhamnosus significantly attenuated lupus-liked disease in lpr mice, by increasing regulatory T cells and balancing T helper-17 cells. Interestingly, we found L. reuteri and an uncultured Lactobacillus spp. were present based on 16S rRNA sequencing. To evaluate the effect of the main candidate L. reuteri in attenuating lupus, we treated lpr mice with the single bacterial strain. Surprisingly, L. reuteri did not reproduce the same results as the Lactobacillus mixture. Thus, we tested the remaining strains individually but none was able to recapitulate the effect of the 5 strains. Additionally, we treated lpr mice with the supernatant of the 5 strains containing secreted metabolites, which did not significantly attenuate lupus. These results suggest that communications among different strains of lactobacilli may be required in ameliorating the disease. Probiotic Lactobacillus spp. may be an alternative treatment against SLE, but further investigations are warranted to delineate the mechanisms of how multiple strains of lactobacilli can exert a beneficial effect as a community.