AUTHOR=Hu Chaowei , Wang Pan , Yang Yunyun , Li Juan , Jiao Xiaolu , Yu Huahui , Wei Yongxiang , Li Jing , Qin Yanwen 

TITLE=Chronic Intermittent Hypoxia Participates in the Pathogenesis of Atherosclerosis and Perturbs the Formation of Intestinal Microbiota

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.560201

DOI=10.3389/fcimb.2021.560201

ISSN=2235-2988

ABSTRACT=Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular disease. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to the pathogenesis of arteriosclerosis (AS) remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE-/-) mice treated with high-fat diet (HFD) and subjected to CIH conditions mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation was confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that induction of CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE-/- mice treated with HFD. Significantly perturbed GM profiles were detected following induction of CIH in AS mice, with altered microbial both α and β diversities and advanced shifts in bacterial compositions at phylum and genus levels. The gut bacteria was significantly varied in AS mice with and without CIH compared with that of the control mice. Reduced abundance of Bacteroidetes and increased Clostridium and Coprococcus species were noted. The correlation of intestinal bacterial parameters across groups indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the disturbance in gut microbial functions and in the potential ability of metabolic pathway modulation was identified to be dependent on CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.