Chronic intermittent hypoxia induces gut microbial dysbiosis and infers metabolic dysfunction in mice

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, and has been associated with adverse metabolic outcomes. There is increasing evidence indicating the important role of gut microbiota in OSA and its comorbidities, while the perturbation of intestinal microbial community elicited by OSA has yet to be well-characterized. Here, we investigated the effect of chronic intermittent hypoxia (IH), a hallmark feature of OSA, on gut microbiota in mice.Male C57BL/6 mice were exposed to a pattern of chronic IH or normoxic conditions for 6 weeks. Fecal samples were collected. The composition of microbiota was determined by 16S rRNA gene amplicon sequencing, and PICRUSt2 was performed to predict functional potential of gut microbiome.In IH mice, accompanied with elevated systemic inflammation, gut microbiota were significantly altered, characterized by enriched Bacteroides, Desulfovibrionaceae and decreased Bifidobacterium. Bacterial operational taxonomic units (OTUs) were clustered into co-abundance groups (CAGs) as potential functional unit in response to IH exposure. One CAG including bacteria of Bacteroides acidifaciens and Desulfovibrionaceae was positively correlated with systemic inflammation in mice, while another CAG composed of bacteria in Muribaculaceae was negatively correlated. Prediction of metabolic pathways showed that, changes in microbiota from IH treatment mainly impacted on bile acid and fatty acid metabolism.Our data demonstrated that dysbiosis of gut microbiome was associated with systemic inflammation and metabolism disorder, and emerges as a mediator for IH and its consequences. Targeting microbiota will be a promising approach to curtail metabolic risks of OSA clinically.