Resistant starch supplementation alters the gut microbial consortium and attenuates kidney inflammation in an experimental model of autoimmune vasculitis

Abstract

Abstract Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare autoimmune disease with suboptimal treatment options which contribute to morbidity and mortality. The characteristic pathological feature is severe inflammation induced by neutrophils which causes life threatening damage to the small blood vessels of the kidney. Neutrophil activity is influenced by microbial metabolites, including short chain fatty acids (SCFAs), produced from fermentation of non-digestible carbohydrates by gut microbiota. We utilised a well-established mouse model of AAV. Mice were randomised to receive either a control diet or a diet supplemented with 15% resistant starch (RS) (n=8 per group). At day 20, mice were culled and kidneys removed to assess injury. Glomerular neutrophil and macrophage infiltration were assessed by immunohistochemistry. Cecal contents were collected, DNA extracted and the V1-V2 hypervariable region amplified using 27F and 338R universal primers to assess the gut microbiota. The resistant starch intervention significantly reduced segmental necrosis in glomeruli (77.63 ± 7.2 % vs 25.59± 4.5 p/gcs, p < 0.0001) and reduced neutrophil (1.3 ± 0.37per glomerular cross section (p/gcs) vs 0.4 ± 0.3p/gcs, p < 0.0001) and macrophage (1.6± 0.3 p/gcs vs 0.4 ± 0.08 p/gcs, p < 0.0001) infiltration into glomeruli. The resistant starch diet significantly altered the gut microbiota consortium and was associated with a substantial expansion of Bacteroidaceae and Muribaculaceae both SCFA producing bacteria. This is the first report of the therapeutic efficacy of a resistant starch supplemented diet in experimental AAV. This data represents a promising therapeutic avenue to limit autoimmune kidney injury in AAV.