The Impact of Gut Microbiota on Immunoglobulin A Nephropathy through the Mediation of Specific Immune Cells: A Mendelian Randomization Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: Gut microbiota alterations had been implicated in the pathogenesis of IgA nephropathy (IgAN). However, how did the gut microbiota participated in the onset and development of IgAN was unclear. This study investigated the causal effects of gut microbiota on IgAN and identifies potential mediators, including lipids, inflammatory factors, metabolites, and immune cells. Methods: Genome-wide association study (GWAS) data for gut microbiota, IgAN, and mediators were analyzed. Two-sample Mendelian randomization (MR) assessed the causal relationship between gut microbiota and IgAN, followed by two-step MR mediation analysis to identify indirect effects via mediators. Mediation effects were quantified using the coefficient product method. Results: MR analysis identified six genera and one phylum of gut microbiota with potential causal linked to IgAN. Two-step MR revealed one lipid, two inflammatory factors, ten metabolites, and sixteen immune cell types as mediators. Specifically, Oscillospira, Clostridium innocuum group, and Actinobacteria exerted effected via IgD+CD24− B cells, CD24 on IgD+CD38+ B cells, and CD4 on naïve CD4+ T cells, respectively. Conclusion: Gut microbiota alterations could causally influence IgAN, with specific immune cell subsets mediating these effects. Specific subsets of B cells and T cells could be involved in the development of IgAN, which would need our attention in the future.
Source: Kidney Diseases
DOI: 10.1159/000549469
Authors: Junli Wan, Mei Yang, Qilin Chen, Shuying Li, Xinyi Ye, Qiu Li
Institution: Children's Hospital of Chongqing Medical University
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,320
OpenAlex ID: W7125507935
