Abstract: PO1432
Gut Microbiome Changes in NZBWF1/J Murine Lupus Nephritis
Session Information
- Glomerular Diseases: Immunology and Inflammation in Vasculitis and Lupus Nephritis
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Chan, Tak Mao Daniel, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
- Yu, Jing, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
- Tai, Chi pang, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
- Yung, Susan, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
Background
Lupus nephritis is an important cause of acute kidney injury and chronic kidney disease. There is preliminary data that gut dysbiosis may be involved in the pathogenesis of lupus nephritis. We investigated gut microbiota burden in murine lupus nephritis.
Methods
Eight-week old NZBWF1/J mice were randomized to receive drinking water alone or containing ampicillin (1.0 mg/ml) and neomycin (0.5 mg/ml) for 18 weeks. Renal and colonic histopathology was examined, and intestinal mucosal permeability investigated with LPS-FITC. Quantitative changes in gut microbiota were assessed by 16S rRNA sequencing.
Results
Serum LPS and urea levels, and proteinuria were significantly lower in antibiotic-treated mice (P<0.05, for all). Histopathologic manifestation of active nephritis and podocyte foot process effacement were associated with increased LPS-binding protein, CD14 and TLR-4 expression in proximal renal tubular epithelial cells, and increased interstitial α-smooth muscle actin, fibronectin and collagen expression. Mice with active nephritis showed increased gut permeability to LPS-FITC given orally, and decreased ZO-1 expression in the colonic epithelium. 16S rRNA sequencing data showed that active nephritis was associated with a progressive decrease in Gram-positive bacteria phyla Actinobacteria and Firmicutes and increased Gram-negative bacteria phyla Bacteroides and Proteobacteria. Antibiotic treatment significantly decreased Bacteroides, which was associated with lower levels of serum LPS and urea, proteinuria, and ameliorated histopathologic features in the colon and kidney.
Conclusion
Murine lupus nephritis is associated with gut dysbiosis, which may contribute to the pathogenesis of nephritis progression.
Funding
- Government Support – Non-U.S.