Exploring the Genetic Link between Gut Microbiome and Tendinopathy: A Mendelian Randomization and Bioinformatics Approach

Abstract This study investigates the genetic link between the gut microbiome (GM) and tendinopathy, identifying shared pathogenic pathways and significant genes. Using a two-sample bidirectional and multivariable Mendelian Randomization (MR) approach, supplemented by bioinformatics analysis, we analyzed summary statistics from genome-wide association studies of gut microbial taxa and data on five tendinopathy phenotypes from the FinnGen database: Achilles, bicipital, shoulder, gluteal, and patellar tendinitis. Genetic data from 23 tendinopathy patients were also analyzed. We found 33 causal relationships between specific gut microbiota and tendinopathies: eight with Achilles, nine with bicipital, five with gluteal, nine with patellar, and three with shoulder tendinitis. Bioinformatics identified 682 differentially expressed genes and 711 genes linked to 28 gut microbiota, with 28 overlapping gene sets. Enrichment analysis highlighted four major gene pathways, and a Protein-Protein Interaction network identified FN1 as a key gene. These findings suggest genetic correlations between gut microbiota and tendinopathies, potentially mediated by FN1 overexpression and regulation of gene pathways, offering new insights into the genetic basis of tendinopathy and the gut microbiome's role in its pathogenesis, informing future therapeutic strategies.