Gut Microbiome in Tendinopathy: Mendelian Randomization and Bioinformatics Therapeutic Targets Study

Abstract

Objective: To explore the relationship between the gut microbiome (GM) and tendinopathy, examining possible shared pathogenic pathways and relevant genes of significant importance. Design:This study employed a two-sample bidirectional and multivariable Mendelian Randomization (MR) approach, supplemented by bioinformatics analysis. Patients: The MR analysis utilized summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n=7738). Data on five different tendinopathy phenotypes were sourced from the FinnGen database, encompassing Achilles tendinitis (AT, n_cases=3113), bicipital tendinitis (BT, n_cases=1317), tendinitis of the shoulder (ST, n_cases=1646), gluteal tendinitis (GT, n_cases=854), and patellar tendinitis (PT, n_cases=439). Genetic data for tendinopathy used in the bioinformatics analysis were derived from 23 patients. Intervention (s): None. Mains Outcome Measure: Incidences of Achilles tendinitis (AT), tendinitis of the shoulder (ST), bicipital tendinitis (BT), gluteal tendinitis (GT), and patellar tendinitis (PT). Result(s): We identified 33 causal relationships between specific gut microbiota (GM) and various forms of tendinitis. Key findings include eight GMs causally related to AT and nine to BT. Five GMs showed significant associations with GT, and another nine with PT. Three specific GMs were significantly associated with ST. Bioinformatics analysis of tendinopathy samples revealed 682 differentially expressed genes (DEGs). We identified 711 genes associated with 28 gut microbiotas after excluding five due to pleiotropy, reverse causality, and unspecified reasons. The analysis identified 682 DEGs and 711 GMs-associated genes, with an overlap of 28 common gene sets (CGS). Enrichment analysis of the 13 CGS identified four major gene pathways. Using a Protein-Protein Interaction (PPI) network, we targeted the key gene FN1. Conclusion (s): Our findings suggest a genetic correlation between 33 GMs and various tendinopathies, potentially mediated by the overexpression of the FN1 gene and the regulation of four gene pathways.