# Gut Microbiome in Patients with Obstructive Sleep Apnoea
## 1 Introduction  
Obstructive sleep apnoea (OSA) is a chronic disease which is characterised by repetitive collapse of the upper respiratory tract during sleep, resulting in chronic intermittent hypoxiaemia and frequent microarousals. OSA is a risk factor for cardiovascular and cerebrovascular disease, with hypertension, dyslipidemia, and enhanced systemic inflammation and oxidative stress being the most investigated mechanisms linking OSA with its comorbidities [1].  
More recently, alterations in the gut microbiome have come into attention as a possible mechanism leading to cardiovascular disease [2]. Certain bacteria may disrupt the gut barrier, facilitating the leakage of bile acids and bacterial toxins, leading to systemic inflammation. In addition, bacterial metabolites such as trimethylamine-N-oxide (TMAO)can enter circulation. Systemic inflammation and TMAO together can lead to foam-cell formation and atherosclerosis [2]. In addition, gut bacteria may produce precursors for neurotransmitters which could affect sleep quality [3].  
Obstructive sleep apnoea may lead to gut dysbiosis via various mechanisms. First, some of the bacteria are oxygen-sensitive [4], and intermittent hypoxaemia in animal models was related to alterations in the gut microbiome and a consequential increase in circulating bacterial toxins and bile acids [3,5,6]. Second, sleep fragmentation in animals and humans is itself also related to gut dysbiosis [3,5,6]. In addition, OSA is related to high fat and high carbohydrate intake [7] which can alter the composition of the gut microbiome [8] and is associated with a pro-atherosclerotic microbiome profile [2].  
Interestingly, the number of studies investigating gut microbiomes in patients with OSA is surprisingly small [9, 10, 11], with only one focusing on adults [11]. Analysing young (2-year-old) snorer and non-snorer children, [PERSON] et al. reported an increased Firmicutes/Bacteroides ratio and a reduced Actinobacteria/Proteobacteria ratio which were hypothesised to relate to later development of comorbidities [9]. In a small (\(n=15\)) pilot study conducted in children (2-12 years old), [PERSON] et al. reported decreased microbial diversity and an increase in gut-barrier-disrupting microbial strains, such as _Proteobacteria_[10]. In adults, [PERSON] et al. reported no difference in relative abundance at the phylum level, but they found significant differences in various genera between the OSA and control groups [11]. Most particularly, they reported a decreased abundance of short-chain fatty-acid-producing bacteria, which could relate to disruption of the gut barrier and consequential increased systemic inflammation [11]. Another report from the same study described that the _Prevotella_ enterotype was the most strongly related to OSA [12]. Of note, the only study in adult humans was conducted in Asian people [11]. As diet is a main factor impacting on the composition of gut microbiome [8,13], these findings cannot be necessarily translated to a Western population.  
The aim of this study was to analyse gut microbiomes in patients with OSA and non-OSA controls, and to compare the results with markers of disease severity and comorbidities.