Abstract MP40: Microbiome-associated Metabolites Are Altered in Mouse Models of Hypertension

Recent studies suggest that the microbiome plays a key role in hypertension and associated inflammation. Microbiota produce metabolites that may lead to activated pro-inflammatory immune cells and contribute to hypertension; however, the altered metabolites in multiple models of hypertension is currently unknown. We hypothesized that there are significant differences in metabolomic profiles between normotensive and hypertensive mice. We utilized two mouse models of hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high salt diet induced hypertension (LSHTN) and angiotensin II induced hypertension (A2HTN). Serum and fecal samples were collected at the end of the treatment period. Ultra-high performance liquid chromatography and tandem mass spectrometry were performed to identify the biochemical composition of each sample. Random Forest Analysis was performed to classify each sample based on similarities and differences in metabolite composition. These procedures were performed by Metabolon, Inc. A total of 1,066 and 1,028 biochemicals were measured in serum and feces, respectively. There were 263 biochemicals in LSHTN serum and 122 biochemicals in A2HTN serum that were statistically different from controls (p≤0.05). There were 298 biochemicals in LSHTN feces and 64 biochemicals in A2HTN feces that were statistically different from controls (p≤0.05). Five biochemical metabolite groups were shown to have significant differences between hypertensive groups and controls: aromatic amino acids, bile acids and sterols, benzoates, fatty acids, and diacylglycerols. Tryptophan metabolites were significantly reduced in the serum of LSHTN mice but not in the serum of A2HTN mice. Serum tyrosine and benzoate metabolites showed varied differences between the two hypertensive groups. Serum fatty acid beta oxidation metabolites were significantly reduced in both hypertensive models but were significantly increased in the feces of mice with LSHTN. In conclusion, this study provided significant analysis of metabolite changes in two hypertension mouse models. Further investigation of the roles these metabolites play in hypertension may lead to targeted therapeutic interventions.