Elsevier

Sleep Medicine

Volume 26, October 2016, Pages 12-15
Sleep Medicine

Original Article
Gut epithelial barrier markers in patients with obstructive sleep apnea

https://doi.org/10.1016/j.sleep.2016.01.019Get rights and content

Highlights

  • The intestinal wall integrity plays a role in the development of metabolic disorders.

  • The influence of obstructive sleep apnea (OSA) on markers of gut barrier was investigated.

  • The I-FABP levels were higher in the presence of OSA.

  • Zonulin levels were associated with metabolic parameters.

  • Obstructive sleep apnea may be a risk factor for intestinal damage, regardless of metabolic profile.

Abstract

Background

Obstructive sleep apnea (OSA) is now being recognized as an additional contributing factor to the pathogenesis of obesity-related comorbidities. At the same time, there is now increasing evidence to suggest that intestinal wall permeability plays a role in the development of metabolic syndrome. In the present study, circulating zonulin and fatty acid binding protein (I-FABP) were measured in association with metabolic, hepatic, and inflammatory parameters.

Results

Compared with controls, plasma I-FABP levels were significantly higher in patients with OSA (571 pg/mL [IQR 290–950] vs 396 pg/mL [IQR 234–559], p = 0.04). Zonulin levels were similar between groups. Significant relationships were observed between zonulin levels and waist circumference (p < 0.05), glucose (p < 0.05), and insulin (p < 0.05). In addition, in the OSA group, zonulin levels correlated negatively with the mean nocturnal oxygenation saturation (p < 0.05) and positively with total cholesterol (p < 0.05), alanine aminotransferase (ALT) (p < 0.005), aminotransferase (AST) (p < 0.01), gamma glutamyltransferase (GGT) (p < 0.005), and high-sensitivity C-reactive protein (hs-CRP) (p < 0.05). Multivariate analysis showed that associations between zonulin and ALT, AST, and hs-CRP were attenuated, but not eliminated, after adjustment for other variables.

Conclusions

The results of this study suggest that OSA is a risk factor for intestinal damage, regardless of metabolic profile, and that intestinal permeability might be a possible contributor to nonalcoholic fatty liver disease in patients with OSA.

Introduction

Obstructive sleep apnea syndrome (OSA) is a common disorder that is defined by the occurrence of repeated episodes of upper airway obstruction and airflow cessation (apneas) that normally lead to intermittent arterial hypoxemia (IH) and sleep disruption [1], [2]. The effects of these cyclical changes of hypoxemia with reoxygenation are similar to ischemia-reperfusion injury, and evidence from both animal and human studies has shown a predominant role of IH in the pathogenesis of OSA comorbidities [3], [4].

Recently, there has been a lot of interest in the role of intestinal wall permeability and gut microbiota in the pathogenesis of obesity and its concomitant disease [5], [6]. Loss of intestinal barrier function or changes in gut microbiota both seem to be key ingredients involved in the pathogenesis of metabolic disorders [7], [8], [9]. In the present study, it was hypothesized that OSA may affect the intestinal barrier function by altering structure and permeability. Repetitive periods of intestinal ischemia reperfusion could result in severe damage to the intestinal barrier, thereby allowing translocation of luminal antigens, bacteria, and their toxic products from the intestinal lumen to the systemic circulation. In addition, persistently increased permeability may be an important contributor to the development of metabolic complications. To test this hypothesis a case–control study was performed and two novel gut barrier markers were evaluated: intestinal fatty acid binding protein (I-FABP) and zonulin. Plasma I-FABP is a highly sensitive marker for intestinal ischemia. Intestinal fatty acid binding proteins are small proteins released into the circulation upon enterocyte membrane integrity loss, which makes them useful as plasma markers for enterocyte damage during the development and progression of intestinal ischemia-reperfusion [10], [11], [12]. By contrast, zonulin is expressed by viable gut epithelial cells to disassemble tight junctions between cells, and increase permeability and macromolecule absorption. Previous studies have claimed a role for zonulin and its regulation of intestinal barrier function in the genesis of metabolic disorders [9], [13], [14].

Section snippets

Subjects and ethics

Patients and controls were recruited from subjects who attended the present sleep unit during a period of two years (2012–2014). In the present study, two subgroups (patients and controls) of participants were retrospectively selected. The final sample comprised 38 patients with OSA and 38 controls matched for sex, age (±5 years), body mass index (BMI) (±3 kg/m), and the presence of metabolic syndrome.

No participant was under continuous positive airway pressure (CPAP) treatment or suffered from

Results

Thirty-eight patients with OSA and 38 control subjects were studied. The main clinical and biochemical characteristics are shown in Table 1. By design, characteristics of patients, including age, sex, BMI, and the prevalence of metabolic syndrome, were similar between patients and controls.

Compared with control subjects, the OSA patients showed elevated plasma levels of I-FABP (Table 1). Participants were divided into three tertiles based on their AHI (AHI <7.5, n = 25; AHI 7.6–28.5, n = 26;

Discussion

This study showed that: (1) the I-FABP levels were elevated in patients with OSA, suggesting that OSA itself is a risk factor for intestinal damage, (2) the zonulin levels were associated with the presence of obesity and metabolic disturbances both in OSA and non-OSA patients, (3) among the OSA patients, zonulin levels were positively correlated with aminotransferases levels, suggesting a possible link between intestinal permeability and nonalcoholic fatty liver disease (NAFLD).

Intestinal fatty

Conclusions

The results of this study showed that I-FABP levels were elevated in patients with OSA, suggesting that OSA itself is a risk factor for intestinal damage. Zonulin levels were associated with the presence of obesity and metabolic disturbances both in OSA and non-OSA patients. In addition, among the OSA patients, zonulin levels were positively correlated with aminotransferases levels, suggesting a possible link between intestinal permeability and nonalcoholic fatty liver disease.

Funding sources

This study was supported in part by Fondo de Investigaciones Sanitarias (Grant number: PI13/02120).

Conflict of interest

All authors declare no conflicts of interest.

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2016.01.019.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

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