Introduction: Obstructive sleep apnoea (OSA) is a common sleep disorder with a high social and economic burden. Thus, early prediction and diagnosis of OSA are important. Changes in metabolism and the microbiome may serve as biomarkers for OSA. Herein, we review the literature on the metabolomic and microbiome changes associated with OSA, and identify the metabolites and microorganisms involved.Methods: We searched the PUBMED and EMBASE electronic databases using the following terms: “obstructive sleep apnea”, “OSA”, “sleep disordered breathing”, “SDB”, “intermittent hypoxia”, “sleep fragmentation”, and either “metabolomics” or “microbiome”. In total, 273 papers were identified, of which 28 were included in our study.Results: Changes in the levels of certain metabolites related to fatty acid, carbohydrate and amino acid metabolism were associated with the incidence of OSA. The diversity and abundance of microflora, particularly Firmicutes and Bacteroidetes, were altered in humans and rodents with OSA.Conclusions: Certain changes in metabolism and the microbiota play an integral role in the pathophysiology of OSA and OSA-induced cardiovascular complications. Metabolomic and microbiome biomarkers shed light on the pathogenesis of OSA, and facilitate early diagnosis and treatment.

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.

Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, c...

Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.