Characterization of fecal metabolome changes in patients with obstructive sleep apnea

Abstract

Study Objectives: Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, intermittent hypoxia during sleep, and increased risk for morbidity and mortality of affected patients. The gut microbiome plays a key role in OSA pathogenesis, and fecal metabolic profiling reflects the gut microbial functional readout and mediates host–microbiome interactions. Methods: Herein, we conducted a cohort study to explore fecal metabolic signatures distinguishing OSA (44 patients) from healthy controls (22 healthy controls) by untargeted gas chromatography–time-of-flight mass spectroscopy. Results: Significant metabolic signatures were detected in stool samples of patients with OSA: 246 metabolites of 24 ontology classes were identified, and 48 metabolites of 6 ontology classes were shifted. An enrichment of arachidonic acid, docosahexaenoic acid, and 11Z-eicosenoic acid and reduction in stearic acid, 5-hydroxyindoleacetic acid, gluconic acid, and a-hyodeoxycholic acid were observed in stool samples from patients with OSA. Fecal variance resulted in alterations in potential metabolic activities and was thereby strongly associated with host phenotypes, such as pulse blood oxygen saturation and apnea-hypopnea index. The prediction model based on feces metabolomics was established to distinguish OSA from healthy controls with high accuracy. Conclusions: This study revealed the metabolomic signatures of patients with OSA in feces, and the findings provide evidence of an association between metabolome and OSA.