Abstract 027: Intestinal Permeability and Dysbiosis are Linked to Hypertension

Introduction: Emerging evidence implicates the involvement of intestinal microbiota in overall physiological homeostasis. Altered microbial composition is associated with metabolic, cardiovascular, and neurological diseases. However, the role of intestinal microbiota in blood pressure control and hypertension (HTN) remains unexplored. The present study was designed to evaluate the hypothesis that both intestinal dysbiosis and altered intestinal function are critical pathophysiological events in HTN. Methods: 16S ribosomal DNA from fecal samples from SHR and chronic angiotensin II (Ang II, 200ng/kg/min) rat models was utilized to compare gut microbial communities between normotensive and hypertensive animals. Gut permeability was assessed by accumulation of FITC-dextran (44mg/100g BW) in the plasma 4 hours following oral feeding. Ex vivo atomic force microscopy was used to determine small intestine and colon stiffness (a measure of permeability). Tight junction gene expression was quantified by qPCR. Results: We observed a significant decrease in microbial richness (20%), diversity (12%), and evenness (10%) in SHR vs WKY. This was associated with an increased Firmicutes (F)/Bacteroidetes (B) ratio (4±1 vs 24±5), a hallmark of gut dysbiosis. Additionally, we observed a 95% increase in plasma FITC-dextran in SHRs (1777±428 vs 3514±563 ng/ml, p Ocln , Tjp1 , and Cldn4 . In addition, we found increased stiffness of both small intestine and colonic tissue, as evidenced by increased elastic modulus in SHR (small intestine: 21.2±3 vs 53.7±8 kPa, colon: 15.7±2 vs 53.4±14 kPa, p Conclusions: These observations show that increased gut permeability/leakiness and dysbiosis is associated with HTN. They are the first to demonstrate a profound intestinal pathophysiology and microbial dysbiosis in HTN.