Multi-Omics Screening and Validation of Gut Microbiota and Risk Genes in Idiopathic Inflammatory Myopathies

The gut microbiota has emerged as a potential therapeutic target for autoimmune diseases, but its role in inflammatory myopathies remains unclear. Integrating Mendelian randomization, database screening, molecular docking, and in vitro experiments, this study computationally nominates Lachnoclostridium as a candidate risk microbe and ENO1 as a candidate risk gene for inflammatory myopathies. Lachnoclostridium and Fusobacterium nucleatum may exhibit potential interactions within the gut microbial community. Molecular docking predicted a binding affinity between ENO1 and a Lachnoclostridium -associated metabolite (− 7.9 kcal/mol). In vitro, ENO1 knockdown in C2C12 myotubes significantly attenuated interferon-gamma-induced secretion of CXCL10 and CCL2 (52% and 57% reduction, both p < 0.01), chemokines critical for immune cell recruitment. Immune infiltration analysis suggested a positive correlation between ENO1 expression and CD8-positive T cell as well as macrophage infiltration in patient muscle. This study provides computational and experimental evidence that ENO1 positively regulates interferon-gamma-induced chemokine secretion in muscle cells, suggesting a potential microbe–gene–immune axis in inflammatory myopathies that warrants further validation.