Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study

Area of Science:

• Genetics
• Microbiology
• Nephrology

Background:

• Therapeutic targeting of the gut microbiota (GM) shows promise for IgA nephropathy (IgAN) prevention and treatment.
• Previous studies indicated a correlation between GM and IgAN, but lacked causal evidence.

Purpose of the Study:

• To investigate the causal relationship between the gut microbiota and IgA nephropathy using a bi-directional Mendelian randomization approach.
• To identify specific gut bacterial taxa causally associated with IgAN.

Main Methods:

• Utilized genome-wide association study (GWAS) data for GM (MiBioGen) and IgAN (FinnGen).
• Employed the inverse variance weighted (IVW) method as the primary analysis, supported by MR-Egger and weighted median methods.
• Conducted sensitivity analyses including Cochrane's Q test, MR-Egger, and MR-PRESSO to assess heterogeneity and pleiotropy, alongside Bayesian model averaging (MR-BMA) for result validation.

Main Results:

• Genus Enterorhabdus was identified as a protective factor for IgAN (OR: 0.456, p=0.023).
• Genus Butyricicoccus was identified as a risk factor for IgAN (OR: 3.471, p=0.0008).
• Sensitivity analyses indicated no significant heterogeneity or pleiotropy.

Conclusions:

• Established a causal link between specific gut microbiota taxa and IgAN.
• Identified Enterorhabdus and Butyricicoccus as potential biomarkers for IgAN.
• These findings advance the understanding of the gut-kidney axis and may inform targeted IgAN therapies.