Abstract 095: Obstructive Sleep Apnea Induced Gut Dysbiosis Stimulates A Proinflammatory Response In Gut And Brain That Contribute To Hypertension

Abstract

Objective: Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension (HT). OSA induces gut dysbiosis, and a dysbiotic microbiota is causal in the development of HT. The mechanisms linking gut dysbiosis to blood pressure (BP) regulation remain unclear. Gut dysbiosis can induce a pro-inflammatory response of the host resulting in peripheral- and neuro-inflammation, key factors in the development of HT. We hypothesized that OSA induced gut dysbiosis elicits a pro-inflammatory response that promotes neuroinflammation and HT. Methods: OSA was induced in 8-week-old male rats (60 apneas/hr for 8 hrs during sleep) by inflating a tracheal balloon. Sham rats underwent balloon implantation without inflations. After 2 weeks of apneas, lymphocytes were isolated from brain, cecum, ileum, mesenteric lymph node (MLN), and spleen for flow cytometry. The role of IL-17 was tested by treating rats with a monoclonal antibody to IL-17 to neutralize circulating IL-17. To track the distribution of lymphocytes originating from the gut, cells in the Peyer’s patches of the small intestine were labelled by injection of carboxyfluorescein succinimidyl ester (CFSE) dye. Results: Following 2 weeks of OSA we found a significant decrease in anti-inflammatory regulatory T (Treg) cells along with an increase in T H 17 (IL-17+) in the brain, cecum, and ileum (n=7, p<0.05 for each). To examine the role of T H 17, we injected an IL-17 neutralizing antibody or control IgG during the 2 weeks of OSA. Compared to OSA rats receiving IgG control, neutralization of IL-17 significantly reduced BP of OSA rats (n=6, p<0.05). IL-17 neutralization also resulted in a significantly increased Tregs and decreased Th1 cells in brain, cecum and ileum of OSA rats (n=6, p<0.01 for each). To examine the distribution of lymphocytes originating from the gut, cells in the Peyer’s patches were labelled with CFSE. We observed significant increases in CFSE+ Th1, Th2, and Th17 cells in the brain, MLN and spleen of OSA as compared to sham rats (n=6, p<0.05). Conclusion: OSA induced gut dysbiosis is associated with a pro-inflammatory response in the gut and brain that involves IL-17 signaling. Treatment strategies to prevent gut dysbiosis may prove useful in reducing neuroinflammation and HT.