Abstract: SA-PO190
Gut Dysbiosis and Altered Gut-Derived Metabolites in Patients with Active Lupus Nephritis
Session Information
- AKI: Mechanisms - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Chan, Tak Mao Daniel, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong
- Xu, Sheng, School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
- Yu, Jing, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong
- Ho, Joshua W. K., School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
- Yung, Susan, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong
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. We investigated gut dysbiosis and changes in gut-derived metabolites in LN patients.
Methods
Fecal samples were collected from 69 patients with kidney biopsy-proven Class III/IV±V LN (16 patients with active LN and 53 patients in remission). Age- and sex-matched samples from healthy subjects (n=15), patients with non-renal lupus (n=27), and patients with non-lupus chronic kidney disease (n=37) served as controls. Bacterial DNA was isolated from fecal samples and submitted to Novogene for shotgun metagenomic sequencing at an average depth of 41 million paired end reads with a read length of 150bp. Sequenced reads were processed to remove adapter regions and low-quality bases, and Phix and human contamination were filtered. High-quality reads were taxonomically profiled at different taxonomic levels using MetaPhlAn4. Microbial pathways and predicted metabolite abundance was assessed using HUMAnN3.6 pipeline and MelonnPan respectively.
Results
Three samples (1 LN and 2 non-renal lupus) failed quality control and were removed from analysis. Alpha and beta diversity were comparable between LN patients and controls. Active LN was accompanied by an increase in the abundance of Megamonas funiformis and Ruminococcus torques and a decrease in Candidatus Avimicrobium caecorum and Alistipes shahii compared to LN patients in remission and control groups (P<0.05, for all). Microbial pathways were similar in patients with active LN and remission, whereas fatty acid β-oxidation, hexitol degradation, ornithine degradation, and NAD salvage pathways were enriched in LN patients compared to healthy subjects. Analysis of microbiota-derived metabolites showed increased abundance of ADMA and chenodeoxycholate, and downregulation of pyridoxamine and nicotinic acid in patients with active LN compared to remission (P<0.05, for all).
Conclusion
LN is associated with gut dysbiosis and altered metabolite abundance. Whether these changes are of pathogenic significance remains to be established.
Funding
- Government Support – Non-U.S.