Background and Aims Systemic Lupus Erythematosus (SLE) is a complex, multifactorial autoimmune disease mediated by the deposition of immune complexes in tissues such as the kidney, skin and brain, with the ensuing inflammatory cascade driving progressive tissue damage and dysfunction. Mice lacking Lyn tyrosine kinase (Lyn^-/- mice) develop an autoimmune disease similar to SLE, driven by dysregulation of the immune system, immune complex deposition in tissue and systemic inflammation culminating in progressive glomerulonephritis. The gut microbiome has been shown to have an immunoregulatory effect on the development of autoimmune and inflammatory diseases, in large part due to the production of short chain fatty acids from the fermentation of dietary fibre.

Methods To determine whether dietary fibre could moderate systemic autoimmune and inflammatory pathology, Lyn^-/- mice and control C57BL6/J mice were fed a high fibre diet (HFD) or a standard control diet from weaning until 42 weeks old.

Results On the control diet, Lyn^-/- mice developed dysbiosis, lymphopenia, splenomegaly from enhanced splenic myelopoiesis, hyperactivation of immune cells, and pathogenic IgG anti-dsDNA autoantibodies that deposited in the kidney glomeruli leading to glomerulonephritis. These hallmarks of inflammation and autoimmune disease were significantly reduced in Lyn^-/- mice fed a HFD, indicating that dietary intervention is effective at dampening chronic systemic inflammation and glomerular pathology.

Conclusions These findings highlights the contribution of diet and the gut microbiome in regulating systemic immune responses and controlling autoimmunity, inflammation, and preventing the progression of immunopathology and suggests that fibre supplementation may improve outcomes for those living with SLE or other chronic systemic inflammatory diseases.