Work

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

Year: 2026

Type: article

Abstract: 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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1796944

Authors: Xinying Liu, Shuo Yang, Yingying Yan, Lin Zhang, Xiaokun Yang, Li Liu

Institution: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine

Language: English

Topic: Inflammatory Bowel Disease

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801