Causal relationship between bladder cancer and gut microbiota contributes to the gut-bladder axis: A two-sample...

Area of Science:

• Microbiology
• Oncology
• Genetics

Background:

• Emerging evidence suggests a connection between gut microbiota and urological tumors.
• The precise causal link between gut bacteria and bladder cancer (BCa), along with the role of metabolic pathways, requires further elucidation.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and bladder cancer (BCa) using a Mendelian randomization (MR) approach.
• To identify specific gut microbial taxa and metabolic pathways involved in BCa pathogenesis.

Main Methods:

• Utilized instrumental variables (IVs) for gut microbiota from large-scale genome-wide association studies (GWAS).
• Employed Mendelian randomization (MR) with inverse variance weighted (IVW) as the primary method to assess causality between gut microbiota and BCa.
• Analyzed metabolic pathways associated with identified microbiota and conducted sensitivity analyses to ensure result validity.

Main Results:

• Identified five gut microbiota taxa causally associated with BCa, with the genus Bilophila showing a notable promoting effect.
• Metabolic pathway analysis revealed significant associations with BCa, particularly implicating amino acid and NAD metabolism.
• Sensitivity analyses confirmed the robustness of the findings, with no significant heterogeneity or horizontal pleiotropy detected.

Conclusions:

• Established a significant causal relationship between specific gut microbiota, notably Bilophila, and bladder cancer (BCa).
• Highlighted the role of amino acid and NAD metabolism in BCa pathogenesis, suggesting potential therapeutic targets.
• Underscored the potential of microbiota-based interventions for BCa prevention and treatment, advancing precision medicine approaches.