Causal relationship between gut microbiota and kidney diseases: a two-sample Mendelian randomization study.

Area of Science:

• Microbiome research
• Renal disease genetics
• Human health

Background:

• The gut microbiome's role in inflammatory kidney diseases like nephrotic syndrome and chronic kidney disease is known.
• However, causal links between specific gut bacterial genera and these renal conditions remain unclear.

Purpose of the Study:

• To investigate potential causal relationships between gut microbial genera and susceptibility to various kidney diseases.
• Utilizing two-sample Mendelian randomization (MR) analyses to establish these links.

Main Methods:

• Genome-wide association study (GWAS) data for gut microbiota and kidney diseases were analyzed.
• Two-sample MR, including inverse-variance weighted (IVW) and MR Egger methods, identified causal links.
• Sensitivity analyses (Cochran's Q, MR-PRESSO) and reverse MR assessed result robustness and reverse causation.

Main Results:

• Significant associations were found between specific gut genera and nephrotic syndrome (12 genera), membranous nephropathy (7), glomerulonephritis (3), acute tubulo-interstitial nephritis (4), chronic tubulo-interstitial nephritis (6), and chronic kidney disease (7).
• Both positive and negative causal relationships were identified, supported by IVW-OR values (P<0.05).
• Sensitivity analyses confirmed the findings, showing no significant heterogeneity or pleiotropy; reverse MR analysis ruled out reverse causation.

Conclusions:

• This study establishes causal associations between specific gut microbial genera and inflammatory kidney diseases.
• Findings enhance understanding of the gut-kidney axis in renal disease pathogenesis.
• These insights can inform early diagnosis and therapeutic strategies for kidney diseases.