Effect of aging on gut microbiota, intestinal permeability and inflammation in a mouse model of obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) can alter the gut microbiome (GM) which may enhance OSA-associated co-morbidities. The prevalence of OSA is increased with age, yet most studies carried out in experimental models were in young animals. Here, we aimed to assess how aging interacts with the negative impact of OSA on GM and intestinal permeability in an intermittent hypoxia (IH) mouse model of OSA. Twenty (2-month old - Y) and 20 (18-month old - O) C57BL/6J mice were investigated. The mice were subjected randomly to either IH or normoxia (N) (10 animals/group) for 6 weeks, after which, fecal and blood samples were collected. Fecal samples were subjected to 16S sequencing followed by bioinformatic analysis. Circulating Zonulin, IL-6, TNF-α and IL-10 levels were assayed with ELISA. Bacterial communities were significantly different in Y and O both under N and IH conditions. Under N, zonulin levels were significantly higher in O than Y mice (p <0.001). Nevertheless, zonulin levels were less affected in O-IH vs. Y-IH (p<0.001). O-N mice had higher levels of IL-6, TNF-α and lower levels of IL-10 compared to Y-N. In addition, O-IH mice showed higher IL-10 (p<0.001) and lower IL-6 (p<0.001) and TNF-α (p=0.002 vs. Y-IH). Correlations between GM elements and inflammatory mediators emerged in different experimental groups. Our results suggest that aging induces important changes to the overall structure of the gut microbial community, which may explain the age group differences observed in basal and IH-induced inflammatory responses and intestinal permeability. These differences may account for the attenuated morbidity impact of OSA in aged patients.