TABLE 2

Obstructive sleep apnoea (OSA) and the microbiome (rodent and human studies)

First author [ref.]	Model	OSA model	Methods	Biofluid	Relative microbial abundance	Results summary
Moreno-Indias [36]	Germ-free C57BL/6 male mice	6 weeks IH	16 S rRNA pyrosequencing	Faecal samples	IH (Family): Lachnospiraceae↑, Prevotellaceae↑, Peptococcaceae↓, Erysipelotrichaceae↓, Bacteroidaceae↓ IH (Genus): Paraprevotella↑, Prevotella↑, Allobaculum↓, Turicibacter↓, Bacteroides↓, Odoribacter↓	Under IH, the intestinal P_aO₂ fluctuated intermittently and the average level decreased The evenness of the microbial community under IH was increased in the intestine
Moreno-Indias [37]	Germ-free C57BL/6 male mice	6 weeks IH followed by 6 weeks normoxic recovery	16 S rRNA pyrosequencing	Faecal samples	IH (Phylum): Firmicutes↑, Deferribacteres↑, Bacteroidetes↓ IH (Family): Ruminococcaceae↑, Desulfovibrionaceae↑, Helicobacteraceae↑, Rikenellaceae↑, Odoribacteraceae↑, Enterobacteriaceae↑, Erysipelotrichaceae↑, Clostridiaceae↑, S24-7↓, Lactobacillaceae↓ IH (Genus): Clostridium↑, Desulfovibrio↑, Sutterella↑, Allobaculum↑, Rikenella↑, Odoribacter↑, Mucispirillum↑, Lactobacillus↓, Ruminococcus↓, Oscillospira↓, Prevotella↓	Decrease of SCFA-producing bacteria and increase of mucin-degrading bacteria could induce a high level of LPS in blood in IH group
Durgan [45]	Rats HFD	Endotracheal obstruction device implantation	16 S rRNA sequencing	Faecal samples	IH+HFD: Clostridiaceae↑, Holdemania↑	In the OSA model, the coexistence of OSA and a HFD could lead to hypertension The ratio of F/B was lower in normal diet OSA group than in the HFD alone group
Ganesh [49]	Rats HFD HFD+Hylon HFD+Clostridium butyricum	Endotracheal obstruction device implantation	16 S rRNA sequencing	Faecal samples	OSA+HFD (Genus): Lactobacillus↑, Allobaculum↑, Bifidobacterium↑ OSA+HFD+C. butyricum (Genus): Dehalobacterium↓, Anaerostipes↓	C. butyricum and Hylon can reduce the effects of OSA on intestinal flora, such as thinning mucosa and a decrease of cecum acetate C. butyricum and Hylon could alleviate OSA-induced goblet cell loss and microglia activation Supplementary acetate in the cecum could prevent OSA-induced hypertension
Tripathi [56]	C57BL/6J male Ldlr^−/− mice HFD	6 weeks IHH	16S rRNA sequencing	Faecal samples	IHH (Family): Clostridiaceae↓, Coriobacteriaceae↓, Lachnospiraceae↑ IHH (Genus): Oscillospira↑	Under the condition of IHH and HFD, mice suffered from intestinal dysbiosis, which led to changes in metabolic profiling, mainly changes in bile acids, phytoestrogens and fatty acids
Lucking [50]	Guinea pig HFD	IH	16 S rRNA sequencing	Faecal samples	IH (Phylum): Firmicutes↓, Bacteroidetes↑	In guinea pigs, the characteristics of cardiopulmonary disease (mainly apnoea and hypertension) in rats induced by CIH exposure were not obvious, but it changed brain stem neurochemistry, reduced the richness of intestinal flora species and changed the composition of flora
Tripathi [57]	C57BL/6J male Ldlr^−/−mice+HFD C57BL/6J male ApoE^−/− mice+HFD	6 weeks (Ldlr^−/−) or 10 weeks (ApoE^−/−) IHH	16S rRNA sequencing	Faecal samples	IHH (Family): Clostridiaceae↓, Lachnospiraceae↑	Under the intervention of OSA, atherosclerosis model involved common microbial and metabolic changes
Liu [46]	Sprague–Dawley rats ND HSD CIH + ND CIH + HSD	6 weeks IH	16S rRNA sequencing	Faecal samples	IH: Lactobacillus rhamnosus↓	Because of the synergistic effect of OSA and HSD, the abundance of lactobacilli in intestine decreased significantly, and the blood pressure increased significantly LGG could prevent the aggravation of hypertension by reducing the level of TMAO, regulating the imbalance of Th1/Th2 cytokines, and inhibiting the phosphorylation of ERK1/2, Akt and mTOR
Poroyko [39]	C57BL/6J mice	4 weeks SF	16S rRNA sequencing	Faecal samples	SF (Phylum): Firmicutes↑, Bacteroidetes↑ SF (Families): Lachnospiraceae↑, Ruminococcaceae↑, Lactobacillaceae↓	SF could lead to increased visceral fat mass and fat tissue inflammation, as wells as systemic insulin resistance and increased leptin plasma levels SF had no effect on aerobic community metabolism, but suppressed anaerobic substrate utilisation
Triplett [40]	Sprague–Dawley rats	6 weeks SF	16S rRNA sequence	Intestinal content	SF ileum (Family): Enterobacteriaceae↓, Lactobacillaceae↓, Turicibacteraceae↑, Clostridiaceae↑ SF caecum (Family): Ruminococcaceae↑, Turicibacteraceae↑ SF colon (Family): Turicibacteraceae, Clostridiaceae, Erysipelotrichaceae↑	Chronic SF significantly increased crypt depth Chronic SF did not trigger systemic inflammation in rats, and microbial extraintestinal translocation and invasion did not occur
Lu [74]	11 OSA and 8 controls (without medical history of systemic disease)	Fibreoptic bronchoscopy	16S rRNA sequencing	BALF	OSA (Phylum): Proteobacteria and Fusobacteria↑, Firmicutes↓	The disruption of pulmonary microbiota in OSA might be the cause of pulmonary inflammation and sensitivity to injury
Xu [25]	30 OSA children and 30 controls (aged 3–11 years old; without medical history of systemic disease)	AHI >1	16S rRNA sequencing Metabolomics	Buccal mucosa	OSA (Family): Veillonellaceae, Campylobacteraceae, C111 Paraprevotellaceae↑ (Genus): Veillonella, Prevotella, Mogibacterium, Campylobacter and Butyrivibrio↑	The oral microbial diversity of paediatric OSA patients decreased, and the microbial structure was different from that of the control group
Ko [72]	126 OSA and 13 controls (without screening of complications)	AHI >5	16 S rRNA pyrosequencing	Buccal mucosa	OSA (Genus): Porphyromonas and Aggregatibacter↑	Compared with non-OSA patients, the relative abundance of Porphyromonas, and the proinflammatory cytokines were higher in patients with OSA
Yang [67]	26 male OSA and 25 male controls (aged 30–65 years; without medical history of systemic disease)	AHI ≥15	16S rRNA sequencing	Oropharynx	Glaciecola was not detected in moderate and severe OSA groups Severe OSA: Tannerella, Anaerovorax and Halomonas ↓	The diversity and abundance of bacteria in the OSA group decreased significantly, and the most significant diversity decline occurred in the moderate OSA group
Wu [73]	472 subjects from the WTCSNORE and 93 subjects from the Zaragoza sleep cohort	AHI ≥5	16S rRNA sequencing	Nasal lavages	Severe OSA (Genus): Streptococcus, Prevotella, Veillonella and Granulicatella↑	The inflammatory mediators in nasal lavage fluid of patients with OSA increased
Ko [54]	93 OSA and 20 controls (without screening of complications)	AHI >5	16S rRNA sequencing	Faecal samples	OSA (Genus): Faecalibacterium↓, Megamonas↓, Ruminococcaceae↓, Clostridiales↓, Alistipes↓, Bifidobacterium↑	Ruminococcus enterotype was associated with increased risk of OSA The level of Lactobacillus was related to the level of homocysteine
Ko [59]	52 OSA and 61 controls (without medical history of gastrointestinal diseases, infection, unexplained diarrhoea, and antibiotics or probiotics used)	AHI ≥15	16 S rRNA pyrosequencing	Faecal samples		The parameters related to sleep were significantly damaged in patients with intestinal type of Prevotella, whose obstructive, central and mixed apnoea index and mean heart rate were also significantly increased

IH: intermittent hypoxia; P_aO₂: arterial oxygen tension; SCFA: short-chain fatty acids; LPS: lipopolysaccharide; HFD: high fat diet; F/B: Firmicutes/Bacteroidetes ratio; IHH: IH and hypercapnia; CIH: chronic intermittent hypoxia; ND: normal diet; HSD: high salt diet; LGG: Lactobacillus rhamnosus GG strain; TMAO: trimethylamine oxide; Th: helper T-cell; SF: sleep fragmentation; BALF: bronchoalveolar lavage fluid; AHI: apnoea–hypopnoea index.