OSA Can Induce Proinflammatory Responses in the Gut, Brain

Obstructive sleep apnea (OSA) can cause a proinflammatory response in the gut and brain, according to study findings published in the Journal of the American Heart Association. 

OSA is an established risk factor for developing hypertension and is also associated with gut dysbiosis. Some studies have shown that the proinflammatory response from gut dysbiosis can lead to peripheral and neuroinflammation. Researchers conducted a study in unanesthetized male rats to determine if OSA-induced gut dysbiosis increases blood pressure. 

All rats included in this study were fed a high-fat diet and then received an endotracheal obstruction device implant. After recovery from implant placement, the rats were separated into 2 groups, with 1 group exposed to apneas and the other group not exposed. The OSA group of rats experienced 60 apneas for 10 seconds at a time per hour for 8 hours. 

Systolic blood pressure was measured using the CODA Volume Pressure Relationship tail-cuff system. The researchers measured at least 10 consecutive readings for each rat. 

On day 14, cecal content was collected from both rat groups and sent to the Center for Metagenomics and Microbiota Research at the Baylor College of Medicine for analysis. The researchers also collected plasma from both rat groups. 

Compared with rats not exposed to apneas, those exposed experienced an increase in blood pressure after 7 (137±5 vs 165±5 mmHg; P =.0044) and 14 (137±4 vs 167±4 mmHg; P =.0012) days.

There were no significant differences in α diversity between the control group and the OSA group when assessing the cecal samples. However, UniFrac distance reports revealed that unweighted (P =.004) and weighted (P =.005) analyses were significant for cecal bacterial community composition. 

The researchers assessed inflammatory status using flow cytometry. After 2 weeks of OSA simulation in the rats, there was a significant reduction in T regulatory cells and an increase in proinflammatory T_H1 and T_H17. 

To determine gut barrier disruption, the researchers assessed inflammation in the mesenteric lymph node (MLN), spleen, and aorta. Analysis revealed significant increases in T_H1, macrophages, and TNF-α+ cells in the spleen, and increased T_H1 and TNF-α+ cells in the aorta.

After 2 weeks of apnea simulation, the researchers assessed neuroinflammation and found a significant decrease in T regulatory cells and increased T_H17, macrophage or microglia, and CD4+ TNF-α+ cells, in the brains of rats with OSA.

Circulating interleukin-17a was elevated rats with OSA compared with control rats receiving nonimmune IgG. A monoclonal antibody was given to neutralize interleukin-17a in rats with OSA to a similar level in control rats. This neutralization reduced gut and brain inflammation.

The researchers also found that lymphocytes originating in the gut can migrate to the MLN, spleen, and brain with increased frequency in rats with OSA.

“Gut dysbiosis may serve as the trigger for gut and neuroinflammation, and treatments to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and hypertension,” the researchers concluded.

Study limitations included the lack of generalizability, not investigating the signals from the microbiota that lead to T-cell activation, and small sample sizes.