Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea–hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea–hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3–4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.
Introduction
Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea‐hypopnea syndrome (OSAHS). Those manifestations independently affect similar brain regions and contribute to OSAHS‐related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that gut microbiota disruption may cross talk the brain function via the microbiota–gut–brain axis. Thus, we aim to survey enterotypes and polysomnographic data of patients with OSAHS.
Methods
Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3–4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined the fasting levels of interleukin‐6 and tumor necrosis factor‐alpha of all subjects.
Results
Three enterotypes
Bacteroides
,
Ruminococcus
, and
Prevotella
were identified in patients with OSAHS. Arousal‐related parameters or sleep stages are significantly disrupted in apnea‐hypopnea index (AHI) ≥15 patients with
Prevotella
enterotype; further analysis this enterotype subjects, obstructive, central, and mixed apnea indices, and mean heart rate are also significantly elevated in AHI ≥15 patients. However, blood cytokines levels of all subjects were not significantly different.
Conclusions
This study indicates the possibility of pathophysiological interplay between enterotypes and sleeps structure disruption in sleep apnea through a microbiota–gut–brain axis and offers some new insight toward the pathogenesis of OSAHS.
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