Gut microbiome-driven mechanisms in inflammatory bowel disease-associated interstitial lung disease: from dysbiosis to therapeutic implications.

Inflammatory bowel disease (IBD) is a chronic, relapsing immune-mediated disorder of the gastrointestinal tract. Interstitial lung disease (ILD) associated with inflammatory bowel disease has been receiving increasing attention. With advances in the gut-lung axis theory, accumulating epidemiological and mechanistic evidence indicates that the association between IBD and ILD is not coincidental or merely driven by drug toxicity, but rather reflects a systemic disease spectrum involving microbiome dysbiosis and cross-organ immune dialogue. This article presents a critical narrative review that systematically summarizes the mechanisms underlying IBD-related ILD, focusing on causal evidence from large cohort and Mendelian randomization studies. It also looks at how gut microbial metabolites remotely regulate lung immune homeostasis, the inflammatory cascades triggered by gut barrier disruption and bacterial translocation, and the therapeutic potential of microbiome-based interventions. This article examines the main limitations and controversies, including the limited accuracy of animal models, the unclear causal link between microbial changes and disease onset, and the challenges in selecting clinical trial endpoints. It also outlines future research directions, focusing on integrating multi-omics, non-invasive diagnostic models, and strategies to distinguish drug-induced lung injury from primary disease involvement. This review aims to elucidate the pathogenesis of this cross-organ disease spectrum and to provide a theoretical foundation for both basic research and clinical translation.