Inulin alleviates intestinal barrier dysfunction induced by chronic intermittent hypoxia by modulating intestinal microbiota in mice

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), disrupts intestinal barrier function and alters gut microbiota composition, leading to systemic inflammation and metabolic disorders. To investigate the protective role of inulin in mitigating CIH-induced intestinal barrier dysfunction and systemic inflammation in mice, with a focus on the underlying gut microbiota-mediated mechanisms. C57BL/6J mice were exposed to CIH for 10 wk with or without inulin supplementation. Intestinal permeability, tight junction protein expression, inflammatory cytokine levels, and gut microbiota composition were assessed by FITC-Dextran assay, ELISA, RT-qPCR, Western blotting, hematoxylin-eosin staining, and 16S rRNA sequencing. The role of gut microbiota was evaluated using an antibiotic intervention. Inulin significantly reduced permeability of intestines, restored protein expression of tight junction, and alleviated histological damage. It lowered transforming growth factor-β, tumor necrosis factor-α, interleukin (IL)-23, -6, and 1β, IL-6 levels, whereas increasing IL-10. Inulin reversed CIH-induced gut dysbiosis, increased microbial diversity, and modulated the Firmicutes/Bacteroidetes ratio. Antibiotic treatment confirmed microbiota-dependent effects. Inulin mitigated dysfunction of intestinal barrier that was induced by CIH and systemic inflammation through modulation of gut microbiota, thus highlighting its potential as a dietary intervention for OSA-related complications.<b>NEW & NOTEWORTHY</b> Inulin alleviates intestinal barrier dysfunction caused by chronic intermittent hypoxia (CIH) in mice. By modulating gut microbiota, inulin reduces systemic inflammation, restores intestinal tight junction proteins, and improves gut health. This research highlights inulin's potential as a dietary intervention to mitigate complications related to obstructive sleep apnea and CIH-induced organ damage.