AbstractIntermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea/hypopnea syndrome (OSAHS). These manifestation 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 microbiota disruption influences the pathophysiological processes of OSAHS through a microbiota–gut–brain axis. Thus, we aim to survey enterotypes and polysomnographic data of OSAHS patients. 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 blood cytokines level of all subjects. Three enterotypesBacteroides(n=73),Ruminococcus(n=14), andPrevotella(n=26) were identified. Central apnea indices, mixed apnea indices, N1 sleep stage, mean apnea–hypopnea duration, and arousal indices were increased in apnea–hypopnea indices (AHI) ≥15 patients with thePrevotellaenterotype. However, for AHI<15 subjects, obstructive apnea indices and systolic blood pressure were significantly observed inRuminococcusandPrevotellaenterotypes, respectively. The present study indicates the possibility of pathophysiological interplay between enterotypes and sleep structure disruption in sleep apnea through a microbiota–gut–brain axis and offers some new insight toward the pathogenesis of OSAHS.ImportanceIntermittent hypoxia (IH) and sleep fragmentation (SF) are hallmarks of are the predominant mechanism underlying obstructive sleep apnea/hypopnea syndrome (OSAHS). Moreover, IH and SF of pathophysiological roles in the gut microbiota dysbiosis in OSAHS have been demonstrated. We hypothesized that gut microbiota disruption may cross-talk the brain function via microbiota–gut–brain axis. Indeed, we observed central apnea indices and other parameters of disturbances during sleep were significantly elevated in AHI≥15 patients with thePrevotellaenterotype. This enterotype prone to endotoxin production, driving systemic inflammation, ultimately contributes to OSAHS-linked comorbidities. Vice versa, increasing the arousal index leads to systemic inflammatory changes and accompanies metabolic dysfunction. We highlight that the possibility that the microbiota–gut–brain axis operates a bidirectional effect on the development of OSAHS pathology.
Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia
