THERAPEUTIC POTENTIAL OF RESISTANT STARCH SUPPLEMENTATION TO MANIPULATE THE GUT-KIDNEY AXIS TO REDUCE RENAL INFLAMMATION IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY VASCULITIS
Diana Yu Shee Tan1, Matthew Snelson2, Anne Cao Le1, Jenny Nguyen1, Melinda Coughlan3, Kim Maree O’Sullivan 1Department of Medicine, Centre for Inflammatory Diseases, Clayton, Victoria, Australia2School of Biological Sciences, Clayton, Victoria, Australia3Department of Diabetes, Prahran, Victoria, Australia
Abstract
Aim: This study aimed to investigate the therapeutic potential of adding resistant starch (RS) to the diet as a supplement in experimental anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). The study hypothesized that RS would be fermented by gut bacteria to produce anti-inflammatory short chain fatty acids (SCFAs) to attenuate inflammation.
Background: AAV is characterised by kidney microvasculature inflammation, leading to glomerulonephritis (GN). SCFAs, produced by gut bacteria, promote gut barrier health but are depleted in inflammatory kidney disease. Restoring gut microbiota dysbiosis could alleviate inflammation by dampening neutrophil activation the critical cell involved in the pathogenesis of AAV.
Methods: We used a well-established model of anti-myeloperoxidase (MPO) GN. Mice were randomised to receive either a control diet or a diet supplemented with 15% resistant starch (RS) (n=8 per group). Kidney injury, glomerular neutrophil macrophage and T cells infiltration was assessed by immunohistochemistry, immune cell populations were assessed by flow cytometry.
Results: Prophylactic treatment with RS-diet significantly reduced 24-hour urinary albuminuria (P<0.05), glomerular injury, neutrophil, CD4 T cells and macrophage recruitment when compared to the control diet (all, P<0.0001). Kidney IL-4 mRNA, lymph nodes and splenic CD4 Th2 cells were all significantly increased in the RS treated group (all P<0.05). Caecal faecal contents were analyzed by 16s rRNA analysis (Illumina Miseq) to determine the composition of the microbiome after diet interventions. Alterations in the gut-microbial consortium was evidenced by expansion of SCFA-producing bacteria Muribaculaceae and Bacteroidaceae and a lower ratio of Firmicutes:Baceriodetes in the RS treated group.
Conclusions: RS supplementation provides renoprotection through expansion of SCFA producing bacteria and correction of gut dysbiosis in MPO-AAV. Dietary supplementation could be a novel adjunct therapy for MPO-AAV.
Biography
Dr Kim O’Sullivan is an Early Career Researcher who heads the Translational Kidney Therapies group at Monash University. Kim’s research program focuses on investigating the pro-inflammatory role of Neutrophil Extracellular Traps (NETs) a form of cell death that promotes inflammation of the small blood vessels which largely affects the kidneys. Kim has a particular focus on looking for potential therapeutics which will prevent NET formation and ameliorate disease-without compromising host defence. Kim currently holds two NHMRC Ideas Grants and an Industry Grant to further her research program.
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