Mechanistic interactions between inflammatory bowel disease and obstructive sleep apnea.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasingly recognized as being associated with obstructive sleep apnea (OSA). Recent cohort studies and meta-analyses identify IBD as an independent risk factor for OSA, supporting the need for OSA screening in patients with IBD and management of modifiable risk factors. However, these associations come primarily from observational studies with virtually no confirmatory mechanistic studies. Further, the available clinical and experimental evidence of an association between OSA and IBD is highly heterogeneous and comes from multidisciplinary sources, suggesting that the association may reflect multiple shared biological mechanisms rather than simple disease coexistence. IBD-associated inflammation, epithelial barrier dysfunction, immune dysregulation, gut dysbiosis, and OSA-associated intermittent hypoxia, oxidative stress, immune activation, gut barrier dysfunction, and gut dysbiosis appear to be the key reciprocal processes establishing a self-reinforcing cycle that links intestinal and respiratory pathophysiology. This theoretical review synthesizes multidisciplinary heterogeneous evidence across clinical, experimental, and mechanistic studies to develop the hypothesis-generating Gut Barrier-Microbiota-Immune-Hypoxia (GBMIH) framework. This hypothesis-generating systems theory highlights intestinal barrier disruption, dysbiosis, immune activation, and intermittent hypoxia as interconnected biological nodes that may mediate this bidirectional relationship and define future biomarker and therapeutic development.