Links between oropharyngeal microbiota and IgA nephropathy: A paradigm shift from isolated microbe to microbiome.

Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally, yet its pathogenesis remains incompletely understood. While much research has focused on the gut microbiome in the development of the disease, emerging evidence suggests that the oropharyngeal microbiota may also be a potential contributor. Studies have revealed significant alterations in oropharyngeal microbial diversity and specific bacterial taxa in IgAN patients, correlating with disease severity and progression. This review aims to comprehensively summarize and discuss the key findings from in vitro, in vivo, and clinical studies into the oropharyngeal bacteria and microbiome alterations in IgAN. Clinical studies have identified associations between certain oropharyngeal bacteria, particularly Cnm⁺Streptococcus mutans, Campylobacter rectus, and Porphyromonas gingivalis with IgAN patients and severe clinical outcomes with. In vitro and in vivo studies further establish a causal relationship between IgAN and oropharyngeal bacteria such as Streptococcus and Haemophilus. Microbiome analyses demonstrate dysbiotic patterns in IgAN patients and identify new potential bacterial genera that have yet to be explored experimentally but may potentially contribute to the disease's pathogenesis. Additionally, the use of these bacterial genera as diagnostic and prognostic biomarkers of IgAN has achieved promising performance. Overall, the evidence highlights the strong connection between oropharyngeal bacteria and IgAN through both causal and non-causal associations. Further investigation into these newly identified bacterial genera and integration of multi-omics data are necessary to uncover mechanisms, validate their role in IgAN, and potentially develop novel diagnostic and therapeutic approaches.