Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP 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 BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP 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 SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
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CD31 immunofluorescence staining of a mesenteric window taken from a rat with liver cirrhosis. In Clinical Science volume 132, Issue 6, Huang et al. use CD31 immunofluorescence staining to show an increased density of the vascular network in the mesenteric window of rats with bile duct ligation-induced liver cirrhosis. Vascular network density is usually low in non-cirrhotic condition, indicating that mesenteric angiogenesis takes place in liver cirrhosis; for details see pages 669–683.
Research Article|
March 30 2018
Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure
Seungbum Kim;
Seungbum Kim
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
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Ruby Goel;
Ruby Goel
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
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Ashok Kumar;
Ashok Kumar
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
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Yanfei Qi;
Yanfei Qi
2Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, U.S.A.
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Gil Lobaton;
Gil Lobaton
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
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Koji Hosaka;
Koji Hosaka
3Department of Neurosurgery, University of Florida, Gainesville, FL, U.S.A.
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Mohammed Mohammed;
Mohammed Mohammed
2Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, U.S.A.
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Eileen M. Handberg;
Eileen M. Handberg
2Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, U.S.A.
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Elaine M. Richards;
Elaine M. Richards
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
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Carl J. Pepine;
2Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, U.S.A.
Correspondence: Carl J. Pepine ([email protected]) or Mohan K. Raizada ([email protected])
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Mohan K. Raizada
1Department of Physiology and Functional, University of Florida, Gainesville, FL, U.S.A.
Correspondence: Carl J. Pepine ([email protected]) or Mohan K. Raizada ([email protected])
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Publisher: Portland Press Ltd
Received:
January 28 2018
Revision Received:
February 21 2018
Accepted:
March 02 2018
Accepted Manuscript online:
March 05 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (6): 701–718.
Article history
Received:
January 28 2018
Revision Received:
February 21 2018
Accepted:
March 02 2018
Accepted Manuscript online:
March 05 2018
Connected Content
A commentary has been published:
Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in cardiovascular disease
Citation
Seungbum Kim, Ruby Goel, Ashok Kumar, Yanfei Qi, Gil Lobaton, Koji Hosaka, Mohammed Mohammed, Eileen M. Handberg, Elaine M. Richards, Carl J. Pepine, Mohan K. Raizada; Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond) 30 March 2018; 132 (6): 701–718. doi: https://doi.org/10.1042/CS20180087
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