Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization

Area of Science:

• Microbiome research
• Urology
• Genetic epidemiology

Background:

• Emerging evidence links gut microbiota to upper urinary tract stones.
• The precise causal relationship remains unclear.

Purpose of the Study:

• To investigate the causal effect of gut microbiome on upper urinary tract stones using Mendelian randomization.
• To identify specific microbial taxa associated with urolithiasis risk.

Main Methods:

• Two-sample Mendelian randomization analysis.
• Utilized large-scale genome-wide association study data for gut microbiome (18,340 samples) and upper urinary tract stones (4,969 cases, 213,445 controls).
• Employed inverse variance-weighted, MR-Egger, maximum likelihood, and weighted median methods, with sensitivity analyses to exclude heterogeneity and pleiotropy.

Main Results:

• Several gut bacteria showed a protective effect against upper urinary tract stones, including Deltaproteobacteria, NB1n, Clostridiaceae1, Barnesiella, Clostridium sensu_stricto_1, Flavonifractor, Hungatella, and Oscillospira.
• Eubacterium xylanophilum was associated with an increased risk of upper urinary tract stones.
• Sensitivity analyses confirmed the robustness of the findings without outlier single nucleotide polymorphisms (SNPs).

Conclusions:

• Established a causal link between specific gut microbial genera and upper urinary tract stones.
• Findings suggest a role for gut microbiota in urolithiasis pathogenesis.
• Further randomized controlled trials are warranted for validation.