Dataset Information

Hypertension-Linked Pathophysiological Alterations in the Gut.

ABSTRACT: RATIONALE:Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension. OBJECTIVE:Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension. METHODS AND RESULTS:Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut-neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology. CONCLUSIONS:A dysfunctional sympathetic-gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.

SUBMITTER: Santisteban MM

PROVIDER: S-EPMC5250568 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Hypertension-Linked Pathophysiological Alterations in the Gut.

Santisteban Monica M MM Qi Yanfei Y Zubcevic Jasenka J Kim Seungbum S Yang Tao T Shenoy Vinayak V Cole-Jeffrey Colleen T CT Lobaton Gilberto O GO Stewart Daniel C DC Rubiano Andres A Simmons Chelsey S CS Garcia-Pereira Fernando F Johnson Richard D RD Pepine Carl J CJ Raizada Mohan K MK

Circulation research 20161031 2

<h4>Rationale</h4>Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension.<h4>Objective</h4>Test the hypothesis that increased sympathetic drive to the gut is associated with increased g ...[more]

PMID: 27799253

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Project description:Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner. Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing. Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension. Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

Project description:Hypertension is the most prevalent risk factor for cardiovascular disease caused by a persistent increase in arterial blood pressure that has lasting effects on the mechanical properties of affected tissues like myocardium and blood vessels. Our group recently discovered that gut dysbiosis is linked to hypertension in several animal models and humans; however, whether hypertension influences the gut's mechanical properties remains unknown. In this study, we evaluated the hypothesis that hypertension increases fibrosis and thus mechanical properties of the gut. A custom indentation system was used to test colon samples from Wistar Kyoto (WKY) normotensive rats and Spontaneously Hypertensive Rats (SHR). Using force-displacement data, we derived an steady-state modulus metric to quantify mechanical properties of gastrointestinal tissue. We observed that SHR proximal colon has a mean steady-state modulus almost 3 times greater than WKY control rat colon (5.11±1.58kPa and 18.17±11.45kPa, respectively). These increases were associated with increase in vascular smooth muscle cells layer and collagen deposition in the intestinal wall in the SHR.Statement of significanceMechanical characterization of biological materials can provide insight into health and disease of tissue. Recent investigations into a variety of cardiovascular pathologies show coincident changes in the microbiome and pathology of the gut. In this study, we sought to quantify changes in the gut in hypertension through mechanical characterization. Our methods and simple models for characterization, adapted from Hertz indentation models, prove useful to identify a meaningful steady-state modulus metric for small and irregular tissues from laboratory animals. Our data, for the first time, establish a stiffening of the gut wall in Spontaneously Hypertensive Rats. This observation suggests significant structural and functional changes in the gut correlate with hypertension, and future experiments are warranted to explore the specific causal relationship between dysbiosis, fibrosis, and stiffening in the gut during the development and maintenance of hypertension.

Dataset Information

Hypertension-Linked Pathophysiological Alterations in the Gut.

Publications

Hypertension-Linked Pathophysiological Alterations in the Gut.

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