Jacquelyn M Walejko1, Seungbum Kim2, Ruby Goel2, Eileen M Handberg3, Elaine M Richards2, Carl J Pepine4, Mohan K Raizada5. 1. Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, FL 32610, United States. 2. Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, United States. 3. Department of Medicine, Division of Cardiology, University of Florida, Gainesville, FL 32610, United States. 4. Department of Medicine, Division of Cardiology, University of Florida, Gainesville, FL 32610, United States. Electronic address: carl.pepine@medicine.ufl.edu. 5. Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, United States. Electronic address: mraizada@ufl.edu.
Abstract
BACKGROUND: Black Americans have greater rates, severity and resistance to treatment of hypertension than White Americans. The gut microbiota and its metabolites may contribute to this. This concept was tested in a pilot study. METHODS: Subjects with high (HBP, >140/80 mm Hg) and normal (NBP, <120/80 mm Hg) blood pressure (BP) provided stool and blood samples for whole genome sequencing (WGS) of gut microbiota and global untargeted metabolomics of serum. Patients were either black (B) with NBP (n = 10 for WGS, 5 for metabolomics) and HBP (n = 10 and 9, BHBP) or white (W) with NBP (n = 20 and 13, WNBP) and HBP (n = 12 and 8, WHBP). RESULTS: All four subject groups had distinct gut microbiota taxonomy by partial least squares discriminant analysis (PLS-DA). More importantly, linear discriminant analysis effect size showed marked differences in function of the microbiota of BHBP and WHBP (PLS-DA) with LDA scores <1. This included pathways for synthesis and interconversion of amino acids and inflammatory antigens. Similarly, metabolites differed (PLS-DA) with BHBP having significantly higher sulfacetaldehyde, quinolinic acid, 5-aminolevulinic acid, leucine and phenylalanine and lower 4-oxoproline and l-anserine. DISCUSSION: Combination analyses of functional gut metabolic pathways and metabolomics data in this small pilot study suggest that BHBP may have greater oxidative stress markers in plasma, greater inflammatory potential of the gut microbiome and altered metabolites with gut microbial functions implying insulin resistance. A fuller understanding of these potential differences could lead to race-based treatments for hypertension.
BACKGROUND: Black Americans have greater rates, severity and resistance to treatment of hypertension than White Americans. The gut microbiota and its metabolites may contribute to this. This concept was tested in a pilot study. METHODS: Subjects with high (HBP, >140/80 mm Hg) and normal (NBP, <120/80 mm Hg) blood pressure (BP) provided stool and blood samples for whole genome sequencing (WGS) of gut microbiota and global untargeted metabolomics of serum. Patients were either black (B) with NBP (n = 10 for WGS, 5 for metabolomics) and HBP (n = 10 and 9, BHBP) or white (W) with NBP (n = 20 and 13, WNBP) and HBP (n = 12 and 8, WHBP). RESULTS: All four subject groups had distinct gut microbiota taxonomy by partial least squares discriminant analysis (PLS-DA). More importantly, linear discriminant analysis effect size showed marked differences in function of the microbiota of BHBP and WHBP (PLS-DA) with LDA scores <1. This included pathways for synthesis and interconversion of amino acids and inflammatory antigens. Similarly, metabolites differed (PLS-DA) with BHBP having significantly higher sulfacetaldehyde, quinolinic acid, 5-aminolevulinic acid, leucine and phenylalanine and lower 4-oxoproline and l-anserine. DISCUSSION: Combination analyses of functional gut metabolic pathways and metabolomics data in this small pilot study suggest that BHBP may have greater oxidative stress markers in plasma, greater inflammatory potential of the gut microbiome and altered metabolites with gut microbial functions implying insulin resistance. A fuller understanding of these potential differences could lead to race-based treatments for hypertension.
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