scholarly journals Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chih-Yuan Ko ◽  
Huan-Zhang Su ◽  
Li Zhang ◽  
Yi-Ming Zeng
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Gut Microbiome ◽  
Mtor Signaling ◽  
Sleep Architecture ◽  
Sequencing Analysis ◽  
Mtor Signaling Pathway ◽  
Obstructive Sleep

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria P < 0.05 , and reduced arginine and proline metabolism pathways P = 0.001 , compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals P < 0.05 . Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway P = 0.006 was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.

Does obstructive sleep apnea confound sleep architecture findings in subjects with depressive symptoms?

2000 ◽  
Vol 48 (10) ◽  
pp. 1001-1009 ◽  
Author(s):  
Wayne A Bardwell ◽  
Polly Moore ◽  
Sonia Ancoli-Israel ◽  
Joel E Dimsdale
Keyword(s):  
Obstructive Sleep Apnea ◽  
Depressive Symptoms ◽  
Sleep Apnea ◽  
Sleep Architecture ◽  
Obstructive Sleep

Abstract P473: Obstructive Sleep Apnea Results In Microbial Bile Acid Biotransformations To Promote Atherosclerosis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Amulya Lingaraju ◽  
Stephany Flores Ramos ◽  
Emily Gentry ◽  
Orit Poulsen ◽  
Pieter C Dorrestein ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Bile Acid ◽  
Sleep Apnea ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Atherosclerotic Lesion ◽  
Farnesoid X Receptor ◽  
Lesion Formation ◽  
Aortic Lesion ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is an independent exacerbator of cardiovascular disease (CVD). However, it is unclear how OSA or it’s characteristic components, intermittent hypoxia and hypercapnia (IHC), increase CVD risk. Our previous work has shown that IHC reproducibly changes the gut microbiome dynamics in murine models of atherosclerosis and that these changes could affect host cardiovascular physiology through bile acids and phosphocholines. In our initial targeted metabolomics approach, changes in particular bile acids, such as taurocholic acid, taurodeoxycholic acid, and muricholic acid, were associated with and were predictive of IHC exposure in atherosclerotic Ldlr-/- mice. In a more recent study, we identified the formation of novel, microbially-synthesized conjugated bile acids by the gut microbiome that are more potent farnesoid X receptor agonists than other previously described bile acids, and thus, potentially can affect atherosclerosis formation. To determine whether these novel bile acids are associated with IHC-induced atherosclerosis, we characterized luminal bile acid changes in Ldlr-/- mice in an OSA model. We hypothesize that IHC alters the amount of microbially-synthesized novel bile acids and that these bile acids are associated with IHC-induced atherosclerosis. To test this hypothesis, we subjected atherogenic diet-fed Ldlr-/- mice to either room-air (control) or IHC conditions (n=10/condition) and assessed atherosclerotic lesion formation after 12 weeks post-diet. Mice under IHC conditions had significantly higher aortic lesion formation compared to controls. Assessment of fecal bile acid metabolites indicated changes in novel bile acid levels under IHC conditions. Moreover, correlational analysis showed that these novel bile acid changes were positively correlated with atherosclerotic lesion amounts, mainly driven by IHC conditions. Our results demonstrate that bile acid changes through microbial biotransformations occur under IHC conditions and could be the mechanistic link between OSA-induced microbiome changes and atherosclerosis.

Postoperative Changes in Sleep-disordered Breathing and Sleep Architecture in Patients with Obstructive Sleep Apnea

2014 ◽  
Vol 120 (2) ◽  
pp. 287-298 ◽  
Author(s):  
Frances Chung ◽  
Pu Liao ◽  
Balaji Yegneswaran ◽  
Colin M. Shapiro ◽  
Weimin Kang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disordered Breathing ◽  
Slow Wave Sleep ◽  
Sleep Architecture ◽  
Secondary Outcome ◽  
Apnea Hypopnea Index ◽  
Postoperative Changes ◽  
Obstructive Sleep ◽  
Disordered Breathing

Abstract Background: Anesthetics, analgesics, and surgery may profoundly affect sleep architecture and aggravate sleep-related breathing disturbances. The authors hypothesized that patients with preoperative polysomnographic evidence of obstructive sleep apnea (OSA) would experience greater changes in these parameters than patients without OSA. Methods: After obtaining approvals from the Institutional Review Boards, consented patients underwent portable polysomnography preoperatively and on postoperative nights (N) 1, 3, 5, and 7 at home or in hospital. The primary and secondary outcome measurements were polysomnographic parameters of sleep-disordered breathing and sleep architecture. Results: Of the 58 patients completed the study, 38 patients had OSA (apnea hypopnea index [AHI] &gt;5) with median preoperative AHI of 18 events per hour and 20 non-OSA patients had median preoperative AHI of 2. AHI was increased after surgery in both OSA and non-OSA patients (P &lt; 0.05), with peak increase on postoperative N3 (OSA vs. non-OSA, 29 [14, 57] vs. 8 [2, 18], median [25th, 75th percentile], P &lt; 0.05). Hypopnea index accounted for 72% of the postoperative increase in AHI. The central apnea index was low (median = 0) but was significantly increased on postoperative N1 in only non-OSA patients. Sleep efficiency, rapid eye movement sleep, and slow-wave sleep were decreased on N1 in both groups, with gradual recovery. Conclusions: Postoperatively, sleep architecture was disturbed and AHI was increased in both OSA and non-OSA patients. Although the disturbances in sleep architecture were greatest on postoperative N1, breathing disturbances during sleep were greatest on postoperative N3.

scholarly journals Sleep Architecture in Night Shift Workers Police Officers with Obstructive Sleep Apnea-hypopnea Syndrome

Sleep Science ◽  
2017 ◽  
Vol 10 (4) ◽  
pp. 134-141 ◽  
Author(s):  
Selene Verde-Tinoco ◽  
Rafael Santana-Miranda ◽  
Romel Gutiérrez-Escobar ◽  
Reyes Haro ◽  
Joana Miranda-Ortiz ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Police Officers ◽  
Night Shift ◽  
Sleep Architecture ◽  
Shift Workers ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

358 Daridorexant Improves Sleep in Patients with Mild/Moderate Obstructive Sleep Apnea

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A143-A143
Author(s):  
Marie-Laure Boof ◽  
Ingo Fietze ◽  
Katharina Lederer ◽  
Anne-Sophie Guern ◽  
Vincent Lemoine ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Duration ◽  
Sleep Onset ◽  
Sleep Architecture ◽  
Sleep Stages ◽  
Apnea Hypopnea Index ◽  
Treatment Difference ◽  
Obstructive Sleep ◽  
Sleep Parameters

Abstract Introduction Daridorexant is a dual orexin receptor antagonist developed for the treatment of insomnia. The effect of the highest phase-3 dose of 50 mg daridorexant on nighttime respiratory function was evaluated in patients with mild/moderate obstructive sleep apnea (OSA). This study showed that repeated doses of daridorexant had no clinically meaningful effect on the apnea-hypopnea index (AHI) or on peripheral oxygen saturation. In the same study, the effect on objective sleep parameters was also explored by polysomnography (PSG). Methods In this randomized, double-blind, placebo-controlled, two-period, crossover study, daridorexant or placebo was administered in each period once daily for 5 consecutive nights to 28 patients. Treatment difference (daridorexant – placebo) for total sleep time (TST), latency to persistent sleep (LPS), and wake after sleep onset (WASO) was analyzed for Night 5 using linear mixed-effects modeling. In addition, sleep was further explored based on sleep duration during each hour of PSG recording, duration of the different sleep phases (rapid eye movement [REM], non-REM [including N1 to N3 sleep stages]), as well as number and mean/longest duration of awakenings. Results Of 28 patients enrolled, 25 completed the study and were included in the analysis (n=15/10 with mild/moderate OSA; mean [standard deviation] AHI: 16.3 [8.2] events/h). One patient had mild insomnia symptoms at baseline. Compared to placebo, daridorexant prolonged mean TST by 38.8 min (90% confidence interval: 19.7–57.9), shortened mean LPS by 17.2 min (-35.5–1.02), and reduced mean WASO by 31.0 min (-47.3 to 14.7). Sleep architecture was maintained as no treatment differences in the duration of the evaluated sleep stages were observed when normalized to TST. Sleep duration was prolonged in the second part of the night. mean and longest duration of awakenings were decreased by a mean (90% CI) of 2.0 min (-3.1 to 0.9) and 16.3 min (-24.1 to -8.6), respectively, without treatment difference for the total number of awakenings. Conclusion Daridorexant improved objective sleep parameters in patients with mild to moderate OSA without modifying sleep architecture. Support (if any) Funded by Idorsia Pharmaceuticals Ltd.

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