Ruminococcus gnavusis a pathobiont expanded by genetic susceptibility and dietary tryptophan in a lupus-prone mouse model

Abstract

Abstract Gut microbial dysbiosis has been associated with the development of systemic lupus erythematosus (SLE). Dietary tryptophan modifies the composition of gut microbiota as well as disease activity in a lupus-prone mouse (TC). To directly test the modulatory function of tryptophan on the gut microbiota, we transplanted the gut microbiota from TC and B6 control mice into germ-free or antibiotic treated B6 recipients fed with high or low dietary tryptophan. Interestingly, a putative human lupus pathobiont Ruminococcus gnavus (Rg) was only enriched in the recipients of TC microbiota fed with high dietary tryptophan, which produced anti-dsDNA IgA and presented T cell infiltration in the kidney. A higher level of Rg was detected in untouched TC mice as compared to B6 controls, in correlation with the levels of lupus signature cytokines. Depletion of this bacterium from the gut of TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, monocolonization of antibiotic-treated TC mice with Rg induced the production of autoantibody as well as increased the frequency of IFN-γ+ T cells, IL-10+ non-T regulatory cells and GC B cells as compared to age-matched TC mice. These results indicate that monocolonization with Rg is sufficient to induce the autoimmune activation in lupus mouse model and that this bacterium is expanded by the combination of lupus genetic susceptibility and tryptophan. This project is supported by grant RO1 AI143313 from the NIH to LMo.