The gut-lung axis: pathological crosstalk and inter-organ communication in chronic obstructive pulmonary disease and...

The significant bidirectional comorbidity risk and extensive subclinical involvement observed between chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) underscore the pivotal role of the "gut-lung axis" in cross-organ pathological crosstalk. Here, we comprehensively review the molecular and immunological mechanisms driving this comorbidity. Genome-wide association studies (GWAS) have substantiated genetic pleiotropy that underpins a shared susceptibility to mucosal defense deficits. The "common mucosal immune system" (CMIS), rooted in embryonic homology, constitutes the anatomical basis for this pathological interplay, wherein aberrant immune cell homing, Th17/Treg imbalance, and the cross-organ trafficking of innate lymphoid cells (ILCs) mediate the distal dissemination of inflammation. Furthermore, gut dysbiosis-induced depletion of short-chain fatty acids (SCFAs), acting in concert with systemic hypoxia and the IL-23/IL-17 axis, potentiates synergistic injury to the gut-lung barriers. We highlight the reciprocal, bidirectional causality of this "hypoxic loop" and its testable mechanistic predictions for barrier dysfunction. Furthermore, we evaluate pharmacological evidence from drug repositioning, alongside a critical examination of the "hidden axis" of clinical therapies as profound iatrogenic confounders. Elucidating these mechanisms is critical for establishing systemic diagnostic and therapeutic strategies; interventions targeting shared molecular targets and the microbiota hold promise for achieving a simultaneous treatment approach for these distinct pathologies.