Inulin Alleviates Intestinal Barrier Dysfunction Induced by Chronic Intermittent Hypoxia by modulating intestinal microbiota in Mice

Background: 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. Objective: 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. Methods: C57BL/6J mice were exposed to CIH for 10 weeks 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, H&E staining and 16S rRNA Sequencing. The role of gut microbiota was evaluated using Antibiotic intervention. Results: Inulin significantly reduced permeability of intestines, restored protein expression of TJ, and alleviated histological damage. It lowered transforming growth factor-β, tumor necrosis factor-α, interleukin (IL)-23, -6 and 1β, IL-6 levels, while increasing IL-10. Inulin reversed CIH-induced gut dysbiosis, increased microbial diversity, and modulated the Firmicutes/Bacteroidetes ratio. Antibiotic treatment confirmed microbiota-dependent effects. Conclusion: 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.

Chronic Intermittent Hypoxia; Gut Microbiota; Intestinal Barrier Dysfunction; Inulin; Obstructive Sleep Apnea.