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Kidney Week

Abstract: TH-PO557

Enhanced Growth of Gut Bacteria Muribaculaceae Reduces Inflammation and Kidney Injury in an Experimental Model of Anti-Neutrophil Cytoplasmic Antibody Vasculitis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • O'Sullivan, Kim M., Monash University, Clayton, Victoria, Australia
  • Snelson, Matthew, Monash University, Clayton, Victoria, Australia
  • Tan, Diana Shu Yee, Monash University, Clayton, Victoria, Australia
  • Nguyen, Jenny, Monash University, Clayton, Victoria, Australia
  • Le, Anne, Monash University, Clayton, Victoria, Australia
  • Huang, U-Shane Stephanie, Monash University, Clayton, Victoria, Australia
  • Coughlan, Melinda T., Monash University, Clayton, Victoria, Australia
Background

The gut microbiome is a critical factor influencing immune homeostasis. Reduced microbial diversity in the gut has been associated with the increasing prevalence of autoimmune diseases. Notably, the family Muribaculaceae has declined within the human microbiome in the industrialised world, and studies have linked its reduced abundance to disease. We investigated the role of the declining Muribaculaceae family in ANCA-associated vasculitis (AAV). We hypothesized that dietary supplementation with resistant starch (RS) a fermentable substrate for gut bacteria would enhance the growth of anti-inflammatory short chain fatty acid (SCFA) producing bacteria (including Muribaculaceae) which would mitigate neutrophil activation and ameliorate kidney inflammation in AAV.

Methods

Using an experimental model of ANCA vasculitis, we assigned mice to treatment groups receiving a diet supplemented with 15% RS (n=8) or a calorie-matched control diet (n=8). Additionally, another cohort of mice was randomized to receive either a control vehicle (n=8), or SCFAs acetate (n=8), butyrate (n=8), or propionate (n=8) orally.

Results

16S rRNA analysis (Illumina miseq) analysis of the caecal contents revealed that the RS diet induced significant alterations in the gut microbiota consortium, characterized by a notable expansion of SCFA-producing bacteria from the Bacteroidaceae and Muribaculaceae families. The ratio of firmicutes/bacteriodota an indication of gut dysbiosis was reversed in the mice on the RS diet. RS treated mice all had significant diminution of inflammation, with a reduction in glomerular injury, neutrophil, macrophage and CD4 T cell recruitment. Mice in the RS treatment group had significantly reduced dendritic cell activation in the draining lymph nodes with a decrease in MHCII and CD80 expression. Albuminuria was significantly decreased in the RS group (p < 0.05). SCFAs alone were not as efficient as RS supplementation in reducing glomerular injury and leukocyte infiltration.

Conclusion

Our findings highlight the therapeutic potential of SCFA production through RS fermentation or direct administration of SCFAs in ANCA vasculitis. These interventions represent possible novel adjunct therapies for reducing inflammation in vasculitis.

Funding

  • Government Support – Non-U.S.