Kidney Week

Abstract: TH-PO0404

Gut Dysbiosis and Increased Abundance of Gram-Negative Bacteria in Humans and Mice with Active Lupus Nephritis

Session Information

• Glomerular Diseases: Autoimmune Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Chan, Tak Mao Daniel, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Tak Mao Daniel Chan, MD, FASN

• Yu, Jing, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Jing Yu, PhD

• Chan, Caleb Chun Yin, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Caleb Chun Yin Chan, PhD

• Xu, Sheng, School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, Hong Kong

Sheng Xu, PhD

• Chu, David H T, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

David H T Chu

• Wong, Cheuk Yin, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Cheuk Yin Wong, PhD

• Ho, Joshua W. K., School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, Hong Kong

Joshua W. K. Ho, PhD

• Yung, Susan, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Susan Yung, PhD

Background

Lupus nephritis (LN) is an important cause of acute kidney injury and chronic kidney disease. Emerging evidence suggests that gut dysbiosis may contribute to LN pathogenesis but the mechanism remains obscure. We previously demonstrated that abundance of Megamonas funiformis and Ruminococcus torques were increased in patients with active LN. We investigated their relationship with clinical and serological disease parameters.

Methods

Bacterial DNA was extracted from the stool of 15 patients with active LN, 52 quiescent LN patients and 15 healthy subjects (HS), and investigated with shotgun metagenomics. NZB/W F1 mice were randomized to receive saline, LPS or antibiotics to assess gut dysbiosis and histopathological changes in the kidney and colon.

Results

Patients with active LN show distinct bacteria composition, with a 6.44-fold increase in Gram-negative bacteria and increased serum LPS level suggesting impaired intestinal epithelial barrier compared with HS. Abundance of Megamonas funiformis correlated with serum IgG level and SLEDAI-2K and renal SLEDAI-2K scores, whereas Ruminococcus torques correlated with anti-dsDNA antibody level, proteinuria and renal SLEDAI-2K score. Abundance of Ruminococcus torques, a Gram-positive bacterium, correlated with superpathway of LPS biosynthesis and serum LPS level in patients with active LN. Superpathway of LPS biosynthesis correlated with SLEDAI-2K score and inversely correlated with C3 level. Active nephritis in NZB/W F1 mice was also associated with increased gut Gram-negative bacteria, and increased serum LPS level. LPS exacerbated histopathologic changes in the colon and kidney in NZB/W F1 mice, with decreased goblet cell number, depletion of tight junctions in colonic epithelial cells, podocyte foot process effacement, proteinuria, and kidney fibrosis. Antibiotic treatment attenuated these abnormalities and reduced the abundance of Ruminococcus genus and Gram-negative bacteria.

Conclusion

We observed increased Gram-negative bacteria in both LN patients and NZB/W F1 mice with active nephritis. Altered microbial pathways relating to LPS biosynthesis was associated with serological and clinical parameters of disease and may contribute to disease activity, kidney inflammation and fibrosis.

Funding

• Government Support – Non-U.S.