Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Recent evidence indicates a link between gut pathology and microbiome with hypertension in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in this study were to test the hypotheses that high blood pressure patients have distinct gut microbiomes and that gut epithelial barrier function markers and microbiome composition could predict systolic blood pressure. Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high blood pressure and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein, lipopolysaccharide, and augmented gut-targeting proinflammatory T helper 17 cells in high blood pressure patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high blood pressure. Zonulin strongly correlated with systolic blood pressure (R2=0.5301, p<0.0001). Two models predicting systolic blood pressure were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of systolic blood pressure from zonulin in plasma (R2=0.4608, p<0.0001). The mouse model of hypertension, chronic angiotensin II infusion, was used to confirm the effects of butyrate and gut barrie...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research