Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy

Area of Science:

• Microbiology
• Nephrology
• Genomics

Background:

• IgA nephropathy (IgAN) is associated with microbial dysbiosis.
• The microbiome's role in IgAN across multiple body sites is not fully understood.

Purpose of the Study:

• To systematically investigate microbial dysbiosis in IgAN patients across various niches.
• To identify potential microbial biomarkers for IgAN diagnosis.

Main Methods:

• Large-scale 16S rRNA gene sequencing was performed on 1,732 samples (oral, pharynx, gut, urine) from IgAN patients and healthy controls.
• Microbial abundance data were analyzed to identify differences between groups and correlations with disease markers.
• Random forest classifiers were developed to predict IgAN status.

Main Results:

• Niche-specific increases in opportunistic pathogens (e.g., Bergeyella, Capnocytophaga) and decreases in beneficial commensals were observed in IgAN patients.
• Similar microbial alterations were noted between early and advanced chronic kidney disease (CKD) stages.
• Oral and pharyngeal bacteria (Bergeyella, Capnocytophaga, Comamonas) correlated positively with creatinine and urea levels.
• Random forest models achieved high accuracy (0.879 discovery, 0.780 validation) in predicting IgAN.

Conclusions:

• This study provides comprehensive microbial profiles of IgAN across multiple body sites.
• Identified microbial signatures show potential as noninvasive biomarkers for IgAN detection and clinical application.