Changes in the gut microbiota in mice exposed to chronic intermittent hypoxia

Introduction. Obstructive sleep apnoea syndrome (OSAS) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic complications, including metabolic and gastrointestinal disorders. Emerging evidence suggests a critical role of the gut microbiota in mediating these effects; however, the impact of CIH on the gut microbiota remains poorly understood. Gap Statement. While CIH is associated with systemic metabolic dysfunction, the specific alterations in gut microbiota composition and function induced by CIH remain understudied. Filling this knowledge gap could elucidate microbiota-mediated mechanisms of OSAS pathogenesis and identify therapeutic targets. Aim. To investigate the effects of CIH on the gut microbiota structure and functional pathways in a mouse model of OSAS. Methodology. Male C57BL/6 mice were exposed to normoxia (NM) or CIH conditions for 6 weeks. Faecal samples were collected via stress defecation before intervention (NM0 and CIH0 groups) and after 6 weeks (NM6 and CIH6 groups). Gut microbiota composition was assessed using 16S rRNA gene sequencing, and functional potential was predicted via Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. Results. A total of 40 faecal samples (10 mice/group) were analysed. No significant differences in microbiota composition, alpha diversity or beta diversity were observed between groups before intervention. CIH significantly altered gut microbiota composition and abundance. At the genus level, Bacteroides abundance increased (rank-biserial=0.558, P =0.014) in CIH6 mice, while Bifidobacterium (Cohen’s d=1.779, P =0.002), Helicobacter (rank-biserial=0.609, P =0.007) and Prevotella (rank-biserial=0.541, P =0.0173) decreased. Linear discriminant analysis effect size (LEfSe) and random forest model analyses identified these genera as key discriminators of microbiota composition. Kyoto Encyclopedia of Genes and Genomes functional prediction revealed 28 significantly altered tertiary metabolic pathways in CIH6 mice, including biotin, lipoic acid, beta-alanine and cyanoamino acid metabolism. Conclusion. CIH induces gut microbiota dysbiosis, disrupts short-chain fatty acid-producing bacteria and impacts multiple metabolic pathways. This study provides evidence linking gut microbiota alterations to OSAS pathogenesis and offers a theoretical foundation for targeting the microbiome as a potential therapeutic strategy for CIH-related disorders.