Background and Aims Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease with environmental and genetic contributing factors. The gut microbiota (GM) interacts with the immune system to maintain homeostasis. However, microbiome dysbiosis has been shown to lead to the development of autoimmune diseases. We aimed to investigate the role of GM in SLE-prone BAFF-Tg mice and study the possible benefit of GM-targeted treatments.

Methods We used 16S metagenomics to compare the GM composition, before or after disease onset, and before or after treatment of established disease with several different fibre-enriched diets or antibiotics. Gut bacteria composition was identified by sequencing V3-V4 regions on an Illumina MiSeq platform in a 96-plex library configuration, and bioinformatics analysis was performed using QIIME software. Matching data on mouse disease levels was obtained by flow cytometry, autoantibody ELISA, and kidney histology.

Results BAFF-Tg mice exhibited distinct GM compositions compared to WT, both before and after disease onset, with certain families of bacteria expanded or replaced prior to disease progression. GM-targeted therapy by high-fibre dietary modulation or antibiotics reduced anti-dsDNA autoantibodies to undetectable levels.

Conclusions GM dysbiosis, of some particular bacterial species we identified, can be linked to the level of disease development in this lupus-prone mouse model. Therapeutic strategies targeting GM, including easily implementable dietary modulations and antibiotics, could be investigated further as novel avenues for treating and managing SLE.