Assessing the Relationship between Gut Microbiota and Kidney Stones: A Two-Sample Mendelian Randomization Analysis

Area of Science:

• Microbiome research
• Genetics
• Nephrology

Background:

• Growing evidence links gut microbiota to kidney stone diseases (KSD).
• A definitive causal relationship between gut microbiota and KSD remains unclear.
• Mendelian randomization (MR) is a suitable method to investigate potential causal links.

Purpose of the Study:

• To assess the potential causal relationship between gut microbiota and kidney stone disease (KSD) risk.
• To identify specific gut bacteria taxa associated with KSD.
• To explore the directionality of the gut microbiota-KSD relationship.

Main Methods:

• Utilized Mendelian randomization (MR) with genetic variants from a genome-wide association study (GWAS) of 18,340 participants for gut microbiota.
• Employed summary statistics from a large GWAS (484,598 cases, 480,873 controls) for KSD.
• Applied inverse variance weighting (IVW) as the primary analysis, with sensitivity analyses including weighted-median, MR-Egger, and MR-PRESSO tests. Reverse MR was also performed.

Main Results:

• Identified suggestive associations between four bacterial traits and KSD risk: class. Lentisphaeria (OR: 0.82), genus. Oscillibacter (OR: 0.79), order. Victivallales (OR: 0.82), and genus. Olsenella (OR: 1.26).
• Sensitivity analyses confirmed the robustness of these associations.
• Reverse MR analysis did not reveal statistically significant associations, suggesting KSD does not causally influence these bacterial traits.

Conclusions:

• Provided evidence supporting a potential causal relationship between four gut microbiota taxa (class. Lentisphaeria, genus. Oscillibacter, order. Victivallales, genus. Olsenella) and kidney stone disease risk.
• These findings highlight specific gut bacteria as potential targets for KSD prevention or treatment.
• Further research is warranted to elucidate the mechanisms by which gut microbiota influences KSD development.