Dysbiosis of the commensal microbiota in IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is a common form of primary glomerulonephritis. Its pathophysiology remains unclear, and no curative treatment has yet been developed. Although abnormal mucosal immune responses to exogenous antigens have been implicated in the onset and progression of IgAN, the mucosal sites responsible for these responses may differ between Asian and Western populations. Furthermore, previous studies investigating the commensal microbiota on mucosal surfaces have identified multiple bacterial taxa that are significantly associated with IgAN; however, few bacterial species have been consistently reproduced across studies. This inconsistency may reflect biological and methodological variations in sample collection, sequencing, and data analysis. Moreover, most previous studies have relied on 16S rRNA amplicon sequencing, which provides a simple and cost-effective means of characterizing microbial community composition but has limited taxonomic resolution and provides little information on microbial function. Recent advances in short- and long-read high-throughput sequencing (HTS) may overcome these limitations by enabling more comprehensive characterization of microbial taxa and functions. In this review, we summarize the current evidence on the gut and oral microbiota in IgAN, discuss the potential mechanisms linking microbial dysbiosis to disease within a microbiota–immune–kidney axis framework, and highlight the methodological considerations and advanced sequencing strategies required for accurate microbiome analysis.