Kidney Week

Abstract: TH-PO0555

Deep Shotgun Metagenomics Reveals Plasmid-Mediated Oral Microbial Mechanisms Underlying Pathogenic IgA Production in IgAN

Session Information

• Glomerular Diseases: IgAN, IgA Vasculitis, and More
  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

• Hamaguchi, Sho, Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Sho Hamaguchi, MD

• Masuoka, Hiroaki, Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Hiroaki Masuoka, PhD, DVM

• Kurokawa, Rina, Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Rina Kurokawa, PhD

• Nihei, Yoshihito, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yoshihito Nihei, MD, PhD

• Mori, Kazuaki, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Kazuaki Mori, MD

• Aoki, Ryousuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Ryousuke Aoki, PhD

• Ogiwara, Kei, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Kei Ogiwara, MD

• Kadota, Nozomi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Nozomi Kadota, MD

• Fukao, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yusuke Fukao, MD

• Suzuki, Hitoshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Hitoshi Suzuki, MD, PhD

• Yamada, Koshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Koshi Yamada, MD, PhD

• Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yusuke Suzuki, MD, PhD

• Suda, Wataru, Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Wataru Suda, PhD

Background

An association between IgA nephropathy (IgAN) and the oral microbiome has long been suggested. In our previous study, we demonstrated that IgA autoantibodies against mesangial cells are produced in the tonsils of IgAN patients, leading us to hypothesize that oral bacteria may induce pathogenic IgA through molecular mimicry between bacterial antigens and mesangial cell components. Therefore, we performed deep shotgun metagenomic sequencing to comprehensively analyze the oral microbiome of IgAN patients and identify microorganisms associated with disease pathogenesis.

Methods

Saliva samples were collected from 57 patients with IgAN, 39 with chronic tonsillitis, and 29 healthy individuals. Shotgun sequencing was performed on extracted DNA. Universal single copy marker genes present in short reads were used to analyze bacterial species and their relative abundances. Additionally, de novo assembly of short reads was conducted to generate contigs, which were classified into three categories—chromosome, plasmid, and phage—based on their genomic features. Subsequently, the diversity and abundance of the contigs were compared among categories.

Results

Shotgun sequencing yielded an average of 67 million paired-end short reads per sample. Analysis of bacterial species identified few bacterial species were consistently enriched in IgAN patients compared to the other groups. However, contig-based analysis revealed that specific bacterial plasmids were significantly increased in IgAN patients. Remarkably, the IgA autoantibodies recognizing mesangial cells, which were established from the tonsils of IgAN patients, specifically recognized one of the host bacterial species carrying these plasmids. Furthermore, the expression level of the antibody-binding protein in the host bacterium was significantly increased in strains isolated from IgAN patients. This finding suggested that the phenotypic change was attributable to plasmid-mediated transformation.

Conclusion

Deep shotgun metagenomic sequencing revealed a significant enrichment of specific bacterial plasmids in patients with IgAN. Furthermore, plasmid-mediated transformation of host bacteria may contribute to the production of pathogenic IgA, suggesting that mobile genetic elements within the commensal microbiome play an important role in the pathogenesis of IgAN.