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 ; 10 9 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.