Exploring the relationship between gut microbiota and spinal canal stenosis: a bidirectional Mendelian randomization and hub gene study across East Asian and European populations.

Abstract

Study design: Mendelian randomization (MR) and gene-level analysis.

Purpose: To investigate the relationship between gut microbiota (GM) and spinal canal stenosis (SCS).

Overview of literature: To date, no studies have demonstrated the relationship between GM and SCS or explored its racial differences.

Methods: This study utilized summary data from publicly available, large-scale genome-wide association studies to investigate the causal relationship between GM and SCS in interracial, European, and East Asian populations using a bidirectional two-sample MR approach. Reverse MR analysis was conducted to estimate the effect of SCS on GM taxa with significant associations. Additionally, genelevel analyses-including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction network analysis-were performed to elucidate key biological processes and hub genes involved in both GM and SCS.

Results: In the interracial population, five bacterial taxa were identified as risk factors and four as protective factors for SCS. Among Europeans, three bacterial taxa were associated with increased risk and three with reduced risk. In the East Asian population, seven bacterial taxa demonstrated protective effects, while one taxon was associated with increased risk. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy. Cross-comparisons indicated significant differences in GM profiles between European and East Asian populations. Gene-level analysis identified key GO terms, enriched KEGG pathways, and hub genes potentially mediating the relationship between GM and SCS.

Conclusion: This study identified a potential causal relationship between GM and SCS, highlighting distinct microbial and genetic mechanisms in European and East Asian populations. The findings provide novel insights into the pathogenesis, prevention, and treatment of SCS. Gene-level analyses suggest potential molecular pathways underlying the GM-SCS association, providing a foundation for future mechanistic research.