scholarly journals Intermittent Hypoxia and Hypercapnia, a Hallmark of Obstructive Sleep Apnea, Alters the Gut Microbiome and Metabolome

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Anupriya Tripathi ◽  
Alexey V. Melnik ◽  
Jin Xue ◽  
Orit Poulsen ◽  
Michael J. Meehan ◽  
...  

ABSTRACTObstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2(hypoxia) and high CO2(hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2and CO2can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences. Here, we model human OSA and its cardiovascular consequence usingLdlr−/−mice fed a high-fat diet and exposed to intermittent hypoxia and hypercapnia (IHH). The gut microbiome and metabolome were characterized longitudinally (using 16S rRNA amplicon sequencing and untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) and seen to covary during IHH. Joint analysis of microbiome and metabolome data revealed marked compositional changes in both microbial (>10%, most remarkably inClostridia) and molecular (>22%) species in the gut. Moreover, molecules that altered in abundance included microbe-dependent bile acids, enterolignans, and fatty acids, highlighting the impact of IHH on host-commensal organism cometabolism in the gut. Thus, we present the first evidence that IHH perturbs the gut microbiome functionally, setting the stage for understanding its involvement in cardiometabolic disorders.IMPORTANCEIntestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders.

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 476
Author(s):  
Bernardo U. Peres ◽  
AJ Hirsch Allen ◽  
Aditi Shah ◽  
Nurit Fox ◽  
Ismail Laher ◽  
...  

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.


mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Celeste Allaband ◽  
Amulya Lingaraju ◽  
Cameron Martino ◽  
Baylee Russell ◽  
Anupriya Tripathi ◽  
...  

People with obstructive sleep apnea, identified by loud snoring and breathing irregularly while sleeping, are at a higher risk of high blood pressure, type 2 diabetes, cardiac arrhythmias, stroke, and sudden cardiac death. We wanted to understand whether the gut microbiome changes induced by obstructive sleep apnea could potentially explain some of these medical problems.


CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 1058A
Author(s):  
Faisal Siddiqui ◽  
Madalina Macrea ◽  
Mitchell Horowitz ◽  
Thomas Martin ◽  
Tomer Pelleg ◽  
...  

ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London

<b><i>Objective:</i></b> The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. <b><i>Methods:</i></b> Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. <b><i>Results:</i></b> By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (<i>p</i> &#x3c; 0.05), while the Apnea-Hypopnea Index (AHI) changed little (<i>p</i> = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all <i>p</i> &#x3c; 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (<i>p</i> &#x3c; 0.05), except with the AHI (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.


2021 ◽  
Vol 4 (1) ◽  
pp. 9
Author(s):  
Esther Oceja ◽  
Paula Rodríguez ◽  
María Jurado ◽  
Maria Luz Alonso ◽  
Genoveva del Río ◽  
...  

Obstructive sleep apnea (OSA) in children is a prevalent, albeit largely undiagnosed disease associated with a large spectrum of morbidities. Overnight in-lab polysomnography remains the gold standard diagnostic approach, but is time-consuming, inconvenient, and expensive, and not readily available in many places. Simplified Home Respiratory Polygraphy (HRP) approaches have been proposed to reduce costs and facilitate the diagnostic process. However, evidence supporting the validity of HRP is still scarce, hampering its implementation in routine clinical use. The objectives were: Primary; to establish the diagnostic and therapeutic decision validity of a simplified HRP approach compared to PSG among children at risk of OSA. Secondary: (a) Analyze the cost-effectiveness of the HRP versus in-lab PSG in evaluation and treatment of pediatric OSA; (b) Evaluate the impact of therapeutic interventions based on HRP versus PSG findings six months after treatment using sleep and health parameters and quality of life instruments; (c) Discovery and validity of the urine biomarkers to establish the diagnosis of OSA and changes after treatment.


2007 ◽  
Vol 293 (4) ◽  
pp. R1666-R1670 ◽  
Author(s):  
Walter T. McNicholas

Considerable evidence is now available of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease. The association is particularly strong for systemic arterial hypertension, but there is growing evidence of an association with ischemic heart disease and stroke. The mechanisms underlying cardiovascular disease in patients with OSAS are still poorly understood. However, the pathogenesis is likely to be a multifactorial process involving a diverse range of mechanisms, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation, and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. Therapy with continuous positive airway pressure (CPAP) has been associated with significant benefits to cardiovascular morbidity and mortality, both in short-term studies addressing specific aspects of morbidity, such as hypertension, and more recently in long-term studies that have evaluated major outcomes of cardiovascular morbidity and mortality. However, there is a clear need for further studies evaluating the impact of CPAP therapy on cardiovascular outcomes. Furthermore, studies on the impact of CPAP therapy have provided useful information concerning the role of basic cell and molecular mechanisms in the pathophysiology of OSAS.


2021 ◽  
Author(s):  
Sofie Jacobs ◽  
Emilie Mylemans ◽  
Marijke Ysebaert ◽  
Eline Vermeiren ◽  
Ann De Guchtenaere ◽  
...  

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