Abstract 007: Obstructive Sleep Apnea Induced Hypertension Involves Gut Dysbiosis and Neuroinflammation
Obstructive sleep apnea (OSA) is an independent risk factor for systemic hypertension, and the most common underlying cause of resistant hypertension. The importance of a healthy gut microbiota on host physiology is becoming increasingly evident. We have shown that gut dysbiosis plays a causal role in the development of OSA-induced hypertension. The mechanisms linking gut dysbiosis to hypertension are unknown. We tested the hypothesis that OSA-induced dysbiosis leads to gut barrier dysfunction, systemic inflammation, and neuroinflammation, which is linked to hypertension. We exposed rats to 2 weeks of sham or OSA (60 apneas/hr). OSA led to a >100-fold increase in TNFα expression in the cecum wall (n=5, p<0.001), and decreased goblet cells/crypt (8.4 vs 11.4; n=6, p<0.05). Consistent with gut barrier dysfunction and bacterial translocation, we found bacterial 16S rRNA in adipose tissue, as well as a 4-fold increase in adipose IL-6 mRNA expression following OSA (n=4-7, p<0.05). Flow cytometric analysis revealed a decrease in the percentage of T-reg cells in the brain of OSA vs. sham rats (0.08% vs. 0.25%; n=3, p<0.05). In addition, the percentage of activated microglia was increased following OSA (20% vs. 10%; n=3, p<0.05). Next, we treated sham and OSA rats with a prebiotic (20% resistant starch diet) or probiotic (C. butyricum; 109 CFU gavage every three days) to increase short chain fatty acids, important in maintaining gut barrier integrity and regulating immune responses. Pre- and probiotic prevented OSA-induced loss of goblet cells and TNFα expression in the cecum. Compared to control rats, pre- and probiotic increased the percentage of T-reg cells in the brain of OSA rats by 10- and 5-fold, respectively (n=3-6, p<0.05 for each). Additionally, pre- and probiotic prevented OSA-induced activation of microglia (n=3-6). Importantly, pre- and probiotic prevented OSA-induced hypertension (prebiotic sham=158.5 vs. OSA=160.3 mmHg, probiotic sham=147.4 vs. OSA=145.6 mmHg; n=6-7, NS). These data demonstrate a causal role for gut dysbiosis in the development of hypertension that involves gut barrier disruption, bacterial translocation, and neuroinflammation. Manipulation of the gut microbiota may serve as a novel therapy in the prevention of hypertension.
Author Disclosures: D.J. Durgan: None. B.P. Ganesh: None. J.W. Nelson: None. R.M. Bryan: None.
This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).
- © 2017 by American Heart Association, Inc.