Abstract
Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.
Highlights
Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease that affects almost 1 billion adults worldwide [1]
The body weight significantly decreased after 2 weeks under Chronic intermittent hypoxia (CIH) in both the chow- and high-fat diet (HFD)-fed groups compared to the control groups (Figure 1B)
Fasting blood glucose (BG) level increased with CIH and HFD interventions, and was higher in the CIH+HFD group compared to the other groups (Figure 1C)
Summary
Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease that affects almost 1 billion adults worldwide [1]. OSA is associated with high economic and health burdens due to the increased risk of cardiovascular and metabolic diseases [2]. CIH and CSF are associated with a wide range of neural, hormonal, thrombotic, and metabolic alterations that promoted OSA-related complications [4–6]. In our previous systemic review, we summarized the changes in the metabolome and microbiota that may play an integral role as intermediary factors in the pathophysiology of OSA and related cardiovascular, metabolic, and neurological complications [7]. CIH and CSF induce dysbiosis of the gut microbial community and serum metabolomics changes. Long-term CSF-induced gut microbiota changes include increased abundances of Lachnospiraceae and decreased abundance of Lactobacillaceae [11]. Few previous studies have comprehensively examined the effects of CIH and CSF on gut microbial composition and function, or the association thereof with host metabolism
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