Article Versions
Export Article
Cite this article
  • Normal Style
  • MLA Style
  • APA Style
  • Chicago Style
Review Article
Open Access Peer-reviewed

Endothelial Dysfunction and Hypertension in African Americans: Overview of the Role of the Gut Microbiome

Marc D. Cook , Lanna Anderson, Maitha Aldokhayyil, Adelola Adeyemo, Mesha Guinyard, Michael Brown
American Journal of Hypertension Research. 2019, 6(1), 1-7. DOI: 10.12691/ajhr-6-1-1
Received April 24, 2019; Revised June 07, 2019; Accepted June 24, 2019

Abstract

Hypertension (now defined by systolic blood pressure/diastolic blood pressure [SBP/DBP] greater than 130/90 mmHg), is one of the most common cardiovascular disorders and is a critical public health and economic concern. African Americans have the greatest burden of hypertension and elucidating the causes of this racial disparity is important for amending and developing effective treatment strategies. Although studies have provided mechanistic insight concerning characteristics of endothelial dysfunction, which likely precedes hypertension in African Americans, our knowledge is limited concerning internal systems (i.e., gut) that may affect endothelial and vascular health outcomes. Recent studies report that the types, and balance, of microbes in the gut are significant contributors to health and disease. Gut microbial dysbiosis, an unhealthy and poorly diverse gut microbial profile, has been linked to hypertension and other diseases that may disproportionately affect cardiovascular health. Relative to hypertension, dysbiosis has been characterized as a reduced richness of short chain fatty acid (SCFA) producing microbes. SCFAs are significant metabolites produced by gut microbes beneficially impact cellular functions, specifically vascular smooth muscle and endothelial cells. Studies concerning the gut microbiome and cardiovascular disease are limited in humans and grossly underrepresent minority populations. This brief review will overview factors concerning the racial disparity in hypertension and provide insight into the potential role that gut dysbiosis may have in hypertension, highlighting the “gut-vascular axis” concerning cardiovascular health.

1. Introduction

Hypertension (as now defined by systolic blood pressure/diastolic blood pressure [SBP/DBP] greater than 130/80 mmHg), is one of the most common disorders and is a critical public health and economic concern. Hypertension increases the risk for cardiovascular disease (CVD) 1, stroke 2, 3, and chronic kidney disease 4 making hypertension a major contributor to death and disability 5. Hypertension is the leading preventable risk factor for premature death and disability worldwide 6. The number of years of life lost to hypertension-related diseases in 2010 was estimated to be: stroke (1.9 million), chronic kidney disease, other cardiovascular and circulatory, and hypertensive heart disease (2.2 million combined), and ischemic heart disease (7.2 million) 7. The overall prevalence of hypertension among US adults from 2015-2016 was 29%, and was similar in men and women 8. The prevalence of hypertension increases with age such that 63.1% among those 60 and older have hypertension 8, 9. Thus, approximately 85 million adults in the US have hypertension and it is estimated that it the prevalence of hypertension will increase by more than 9%, or 27 million more people, from 2010 to 2030 10.

In addition to the US health burden, the economic burden of hypertension is extremely high. Estimates using data analyzed from 2001 to 2005 suggest that hypertension is the costliest of all CVDs, with an estimated direct cost of $69.9 billion in 2010 10. However, when accounting for the prevalence of hypertension in the US society, hypertension is associated with about $131 billion per year in population-level expenditures 11.

In a special issue of Circulation published in 2005, it was reported that significant disparities exist in the prevalence of cardiovascular morbidity and mortality 12. The same is true for a primary risk factor for CVD, hypertension 12, 13. The prevalence, after adjustment for age, is higher in African Americans (AA) than for any other major race or ethnic group 9. Data from the National Health and Nutrition Survey from 1988 to 2008 showed that there were significant increases during this time in the proportions of AA with hypertension compared to their Caucasian (CA) and Hispanic counterparts 9. AA tend to develop hypertension at an earlier age than CA and in children aged 8–17 years, SBP levels were 2.9 mmHg and 1.6 mmHg higher in AA boys and girls, respectively, compared to age-matched CA boys and girls 14.

2. Racial Disparity in Endothelial Dysfunction and Hypertension

While AA race is an independent risk factor for vascular disease 15, 16, current statistics reported in Heart Disease and Stroke Statistics-2019 Update 17 rates show that the burden is yet increasing. The age-adjusted prevalence of hypertension between the years 2011-2016 was reported to be approximately 57% of adult AA men and 53% of AA women affected, compared to 46% and 38% of their CA peers, respectively. Strikingly, the age-adjusted mortality rates attributed to hypertension (per 100,000) in 2016 was 54.0 for AA males and 36.7 for AA females, compared to 21.1 for CA males and 17.3 for CA females. As AA develop hypertension at younger ages than other groups, they are more likely to develop hypertension-associated complications with nearly a two-fold increase in mortality associated with CVD 18 and end-organ damage compared to CA 13. Moreover, hypertension control among treated AA is lower than CA despite the higher awareness in this population 17, 19. In AA men only, one study assessed the economic consequences of men’s health disparities using data from the 2006 through 2009 Medical Expenditure Panel Survey and the National Vital Statistics Reports and found that the total direct medical care expenditures for AA men were $447.6 billion of which $24.2 billion was excess medical care expenditures 20. Thus, revealing the epidemiological racial disparity and public health impact regarding hypertension in AA 21, 22.

In the Jackson Heart Study cohort of AAs, about 34% had masked hypertension which is higher than other population-based studies of other race/ethnicities 23. Our group, and others, have previously reported that masked hypertension was associated with elevated levels of low-grade inflammation and diminished endothelial function in AA 24, 25. Essential hypertension is also associated with abnormal endothelium-mediated vasodilation due to decrease nitric oxide (NO) bioavailability in the endothelium 26, 27. Moreover, endothelium-dependent vasodilation is reduced in normotensive subjects with a familial history of hypertension compared to subjects without a familial history of essential hypertension 28. When assessing vascular function, it was reported that healthy AA exhibited significantly reduced flow-mediated vasodilation (measure of endothelial mediated vascular compliance) compared to their CA counterparts 29, 30.

2.1. Endothelial Dysfunction in AA Hypertension

Endothelial dysfunction consists of the endothelium existing in a chronic low-grade inflammatory state and is marked by an exacerbated immune and oxidative stress response during inflammation (reviewed by Cook M.D. 31). AA have been reported to have greater production of vasoconstricting factors such as endothelin-1 (ET-1) 24 and circulating inflammatory endothelial microparticles 32 (measure of endothelial dysfunction). ET-1 contributes to the development of hypertension and consequent complications by causing systemic vasoconstriction and stimulating the renin-angiotensin system. Concerning endothelial microparticles (EMP), our group has reported circulating EMP burden is associated with hypertension status in multiple publications 32, 33, 34, 35. The higher prevalence of inflammatory-mediated endothelial dysfunction in this population explains, at least in part, the racial disparity in hypertension 36.

In vitro data from our lab, and others, supports the observed racial difference in endothelial dysfunction. AA endothelial cells exhibited greater basal oxidative stress and heightened inflammation compared to CA endothelial cells 15, 37, 38. In Human Umbilical Vein Endothelial Cells (HUVEC) isolated from AA, we reported that AA cells exhibited higher basal expression of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and lower activity of superoxide dismutase (antioxidant capacity) which compromises NO bioavailability 38. Furthermore, AA HUVECs produce higher basal levels of IL-6, an inflammatory cytokine, than CA HUVECs 37, 38. This state of heightened inflammation stimulates the endothelial cells to release EMP that further trigger endothelial dysfunction by disrupting production of NO and reducing endothelial NO synthase (eNOS) activity, promoting coagulation and inflammation 39. We have previously shown that, in response to an inflammatory challenge (Tumor Necrosis Factor (TNF)-α stimulation), AA HUVECs had an increase in EMP generation by 89% compared to 8% in CA, highlighting the detrimental effect of inflammation on AA endothelial cells 37. As endothelial cells are primary cells that make up blood vessels (specifically capillaries which feed our organs), heightened oxidative stress and inflammation initiates a cascade of dysfunctional activities in multiple tissues (i.e., blood vessels, heart, kidneys, intestines, and brain). A reduction in blood vessel function throughout the vascular tree promotes essential hypertension as carotid artery wall thickness and left ventricular mass correlate with reduced endothelium-dependent dilation 40.

Strategies to treat endothelial dysfunction and reduce blood pressure (BP) include drugs targeting the endothelium, such as angiotensin pathway inhibitors, adrenergic receptor blockers, and anti-inflammatory drugs. In a double-blind clinical trial that assessed low-grade inflammation and hemostasis (thrombogenic activity), Ekholm et al. 41 recently reported that both an angiotensin-converting enzyme (ACE) inhibitor and alpha-1 adrenergic receptor blocker reduced BP while reducing thrombin activity and having only minor effects on systemic inflammation. Unfortunately, some drug treatment strategies have been contraindicated in AA (ACE inhibitor therapy) as they lead to worse outcomes 42. With the etiology of AA endothelial dysfunction rooted in basal inflammation, strategies that suppress endothelial inflammation need to be of greater focus. With this, Grimm et al. 43 performed an in vitro study to determine the impact of cyclooxygenase (COX)-1 and COX-2 inhibition in HUVEC (via aspirin and the non-steroid anti-inflammatory drug Celecoxib, respectively). COX is important because it has been shown to regulate prostacyclin (vasodilator) and thromboxane (potent vasoconstrictor) in the endothelium. The balance of prostacyclin/thromboxane regulates vascular homeostasis 44, 45. We reported that COX inhibition alone did not improve inflammatory stimulated reductions in eNOS production. However, COX-2 inhibition improved the prostacyclin/thromboxane ratio as well as a physiologically relevant in vitro exercise mimetic (laminar shear stress) in conjunction with COX-1 and COX-2 inhibition, increased eNOS expression and reduced the prostacyclin/thromboxane ratio. Our in vivo and in vitro data combined support the role of lifestyle interventions (e.g., exercise), and targeted drug therapies, in the maintenance of endothelial health. Lifestyle interventions not only benefit the endothelium but impact a very important tissue that has been noted to impact CV health, the gut microbiome.

3. Gut Microbiome, Endothelial Function, and Hypertension: Current Perspectives

The gut microbiome consists of microorganisms that have been shown to have a profound effect on host health. Gut microbes contribute to nearly every aspect of the human growth and development, predispose one to wellness or disease 46, and constantly adapt their composition according to the host and environment (e.g., age, diet, physiological stress (exercise), psychological stress, and disease) 47. Positively balancing the gut microbial community has been shown to improve CVD risk by reducing cholesterol levels 48, reducing blood glucose and insulin resistance 49, regulating the renin-angiotensin system 50, and lowering BP 51, 52.

Gut dysbiosis is an unhealthy and poorly diverse gut microbial profile which is linked to hypertension 53, 54, and other prevalent health disparities in AA 55, 56. Genetic programming 57, dietary habits 58, 59, environmental stressors 60, and sedentary behavior (e.g., less than 150 minutes of moderate exercise per week) all have a role in the promotion of gut dysbiosis and poorer cardiovascular health 61 in AA. The response of the gut microbes to environment is key to promoting host health. For instance, a diet deficient in fiber promotes an imbalance in gut microbial species that can significantly impact intestinal barrier function and colonic inflammation as microbes’ resort to metabolizing colonic mucus as a source of energy. This phenomenon increases intestinal permeability through the breakdown of this barrier and pathogenic microbes and promotes gut inflammation 62. Gut inflammation is associated with reduced gut SCFA production, poor vascular function, and higher BP 63.

Previous studies have investigated the association of gut flora on the development or control of hypertension when comparing non-hypertensive (control), pre-hypertensive (SBP 120 – 139 mmHg), and hypertensive subjects (SBP ≥140 mmHg). Li et al. 64 reported that control subjects exhibited greater fecal microbial diversity and richness of SCFA producing gut flora comprising of Faecalibacterium, Oscillibacter, Roseburia, Bifidobacterium, Coprococcus, and Butyrivibri. Meanwhile, pre-hypertensive and hypertensive subjects had an underrepresentation of the microbes present in healthy controls and an overrepresentation of Prevotella and Klebsiella. Some species of the genus’ Prevotella and Klebsiella are opportunistic pathogens associated with infection, gut inflammation, and antibiotic resistance 65, 66. Individuals with pre-hypertension and hypertension had significantly lower levels of endogenous 3,4,5-tri-methoxycinnamic acid, among other compounds 64. 3,4,5-Trimethoxycinnamic acid is of particular interest as it has been shown to have anti-inflammatory properties by suppressing the expression of vascular endothelial cell adhesion molecules 67. This compound naturally occurs and has been shown to be metabolized and degraded by gut microbes 68 which suggests that gut dysbiosis associated with elevated BP impacts circulating mediators of vascular health.

3.1. Beneficial Metabolites of Gut Microbial Health

SCFA’s are the main product of gut microbial fermentation of dietary non-digestible carbohydrates. The majority of SCFA’s consist of products ranging from 1-5 carbon (C) molecules and include acetate (2C), propionate (3C), and butyrate (4C). These molecules impact physiological and cellular processes in the gut and systemically. SCFA are absorbed in the small and large intestines, processed by the liver, and released into the systemic circulation if they are not immediately metabolized in the colon. Morrison and Preston 69 provide an excellent review of SCFA and their impact on human metabolism and Pevsner-Fischer et al. 70 report the potential role of the microbiome and BP interactions.

SCFA have anti-inflammatory properties throughout the body. One of the most potent SCFA, butyrate, is important in colon health as it is a significant source of fuel for colonic epithelial cells (colonocytes), regulates cell differentiation, and prevents colon cancer 71. In a small study including AA, Hispanic, and CA individuals, Hester et al. 55 reported that AA had significantly lower levels of fecal butyrate, acetate, and total fecal SCFA that may be related to AA increased risk and incidence of colon cancer. Further, another study reported that lower SCFA gut microbes were significantly related to glucose tolerance and vitamin deficiency in AA 56. O’Keefe et al. 72 reported lower SCFA in AA compared to native Africans. These findings distinguish a link between gut dysbiosis and chronic disorders in AA.

SCFAs produced in the gut have been shown to influence BP 73 and significantly improve endothelial inflammation 74. Butyrate, a SCFA, is of interest as it has anti-inflammatory and anti-atherogenic properties in EC 74. Indeed, intestinal cells are the largest consumers of butyrate produced in the gut. However, Van der Beek et al. 75 has shown that intestines release butyrate into the circulation and the liver facilitates measurable amounts in the blood, likely directly proportional to the amount produced in the gut.

A practical intervention by Wilck et al. 76 reported that increased salt intake elicited a depletion in Lactobacillus species and was associated with an increase in gut pro-inflammatory immune cell expansion (T-helper 17) with a concomitant increase in BP in animals and humans. Probiotic strains, such as Lactobacillus species, produce SCFA 77. Lactobacillus, along with Bifidobactera species, are the majority of most probiotic supplements offered. Their relative abundance, partly due to their role in producing SCFA, are becoming an important marker for gut microbial health.

3.2. Interactions between Vascular Health, the Gut Microbiome, and Exercise

Exercise, a powerful lifestyle modification that impacts vascular health, also influences gut microbial characteristics that promote health in animals 78 and humans 79, 80. Concerning vascular health, Brown et al. 81 discussed the rationale for race dependent exercise-induced changes in endothelial function. Babbitt et al. 32 reported that aerobic exercise training improved endothelial function while reducing circulating inflammatory markers and EMP in AA with hypertension. Increased shear stress on the vascular endothelium (e.g., increased blood flow through the large and small resistance vessels) is a well-documented mechanism associated with improved endothelial function. Additionally, the anti-inflammatory effects of exercise have been documented and further improve vascular health and reduce disease burden 82. However, recent discoveries suggest a role for exercise-induced changes in gut microbial characteristics for improvements in endothelial function and inflammatory burden.

Mailing et al. 80 thoroughly reviewed the currently known associations of gut dysbiosis with disease (i.e., colorectal cancer, inflammatory bowel disease, obesity and metabolic disease, and mental health and cognition) and the influence of exercise on the gut microbiome structure and function. In humans, exercise impacts the gut microbiome structure (e.g., increasing diversity and abundance of species) and function (i.e., increasing metabolic capacity for macronutrient turnover, increasing SCFA producing microbes and capacity to generate SCFA). Currently, most studies have been cross-sectional analyses in Athletic and active populations and very few assess or control for dietary intake 80. In a 6-week (3 day/week; 30-60 min/day) exercise intervention of college-aged lean and obese subjects that controlled for dietary intake before fecal sample collection, we reported that exercise significantly increased the abundance of SCFA producing microbes, SCFA producing capacity (via butyryl-CoA: acetate CoA-transferase (BCoAT) and methylmalonyl-CoA decarboxylase (mmdA) concentrations), and SCFA concentrations in fecal samples 79. BCoAT and mmdA are two pathways that contribute to the production of butyrate and propionate, respectively. After a post-intervention 6-week wash-out period where participants performed no exercise, the gut microbiome adaptations were lost. Increasing the capacity of the gut to produce anti-inflammatory metabolites (via exercise), such as butyrate, adds another potential mechanism by which exercise may improve CV health risk factors outlined previously in this review. Future studies are needed to assess these associations to identify specific species associated with inflammation and BP specifically in AA.

3.3. Medication and the Gut Microbiome

Medications prescribed for the management of BP target multiple pathways related to the perceived root causes of high BP which include endothelial dysfunction, vascular smooth muscle function, sympathetic nervous system blockers, and enzyme inhibitors. Wilson and Nicholson 83 reviewed the current work that outlines the relationship between the gut microbiome in the metabolism, toxicity, and biotransformation of drugs into their active forms. As the gut microbial community establishes itself to acutely or chronically metabolize drugs, it also adapts to remove byproducts of those processes (i.e., detoxify). Contingent on those byproducts, the shift in gut microbial characteristics may promote an environment that has negative consequences on other biological processes related to macronutrient (eg., fat, glucose, and protein) and micronutrient (e.g., vitamin and mineral) metabolic pathways in tissues and organs 83. These changes may also elicit unintended side-effects. For example, the non-response and side-effects to ACE inhibitors in AA are noted but it is not known whether gut microbiome has a role in promoting ACE inhibitor therapy ineffectiveness and side-effects in this population. Therefore, efforts to understand the role of chronic medication, such as those related to BP treatment, on gut microbial patterns related to health and disease is essential. With this, the future of drug-managed treatment of chronic disorders will likely include individualized treatment strategies that utilize gut microbial adaptations to drugs to outline their relationship to overall health of the gut microbiome and host.

4. Conclusion

With AA carrying the greatest burden of hypertension and hypertension associated morbidity and mortality, therapies that target the etiology of this CV dysfunction in AA are essential. Research implies that an anti-inflammatory gut microbial profile (i.e., greater SCFA production capacity) would parallel the reduction in systemic low-grade inflammation associated with basal endothelial dysfunction and hypertension status. Future studies should include assessment of interactions between hypertensive medication(s) that initiate drug-induced changes in gut microbial characteristics that may impact drug efficacy (non-response to certain treatments), side-effects, and additional health outcomes. Advocacy to promote the reduction in hypertension should include strategies that improve SCFA capacity in the gut (e.g., exercise and dietary fiber) to suppress low-grade systemic and endothelial inflammation to improve BP control and CV outcomes.

Acknowledgements

Publication of this review is supported by American Heart Association (AHA) Career Development Award (CDA) 18CDA34110444 awarded to Marc Cook. All authors have given consent for publication of this work and we declare there are no competing or conflicting interests.

References

[1]  Kjeldsen, S.E., Hypertension and cardiovascular risk: General aspects. Pharmacol Res, 2018. 129: p. 95-99.
In article      View Article  PubMed
 
[2]  Dad, T. and D.E. Weiner, Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages. Semin Nephrol, 2015. 35(4): p. 311-22.
In article      View Article  PubMed  PubMed
 
[3]  Lawes, C.M., et al., Blood pressure and stroke: an overview of published reviews. Stroke, 2004. 35(4): p. 1024.
In article      View Article  PubMed
 
[4]  System, U.S.R.D., Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, in USRDS Annual Data Report. 2009, National Institute of Diabetes and Digestive and Kidney Disease.
In article      
 
[5]  Murray, C.J., et al., The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA, 2013. 310(6): p. 591-608.
In article      View Article  PubMed  PubMed
 
[6]  Mills, K.T., et al., Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation, 2016. 134(6): p. 441-50.
In article      View Article  PubMed  PubMed
 
[7]  Egan, B.M., et al., Hypertension in the United States, 1999 to 2012: progress toward Healthy People 2020 goals. Circulation, 2014. 130(19): p. 1692-9.
In article      View Article  PubMed  PubMed
 
[8]  Fryar, C.D., et al., Hypertension Prevalence and Control Among Adults: United States, 2015-2016. NCHS Data Brief, 2017(289): p. 1-8.
In article      
 
[9]  Egan, B.M., Y. Zhao, and R.N. Axon, US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA, 2010. 303(20): p. 2043-50.
In article      View Article  PubMed
 
[10]  Heidenreich, P.A., et al., Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation, 2011. 123(8): p. 933-44.
In article      View Article  PubMed
 
[11]  Kirkland, E.B., et al., Trends in Healthcare Expenditures Among US Adults With Hypertension: National Estimates, 2003-2014. J Am Heart Assoc, 2018. 7(11).
In article      View Article  PubMed  PubMed
 
[12]  Carnethon, M.R., et al., Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association. Circulation, 2017. 136(21): p. e393-e423.
In article      View Article  PubMed
 
[13]  Ferdinand, K.C. and R.R. Townsend, Hypertension in the US Black population: risk factors, complications, and potential impact of central aortic pressure on effective treatment. Cardiovasc Drugs Ther, 2012. 26(2): p. 157-65.
In article      View Article  PubMed
 
[14]  Muntner, P., et al., Trends in blood pressure among children and adolescents. JAMA, 2004. 291(17): p. 2107-13.
In article      View Article  PubMed
 
[15]  Kalinowski, L., I.T. Dobrucki, and T. Malinski, Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases. Circulation, 2004. 109(21): p. 2511-7.
In article      View Article  PubMed
 
[16]  Hozawa, A., et al., Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects--Atherosclerosis Risk in Communities Study. Archives of internal medicine, 2007. 167(6): p. 573-9.
In article      View Article  PubMed
 
[17]  Benjamin, E.J., et al., Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, 2019. 139(10): p. e56-e528.
In article      
 
[18]  Go, A.S., et al., Heart disease and stroke statistics--2014 update: a report from the american heart association. Circulation, 2014. 129(3): p. e28-e292.
In article      
 
[19]  Egan, B.M., et al., Hypertension in the United States 1999–2012: Progress Toward Healthy People 2020 Goals. Circulation, 2014. 130(19): p. 1692-9.
In article      View Article  PubMed  PubMed
 
[20]  Thorpe, R.J., et al., Economic Burden of Men's Health Disparities in the United States. International Journal of Men's Health, 2013. 12(3).
In article      View Article
 
[21]  Ferdinand, K.C. and A. Armani, Cardiovascular Disease in Racial and Ethnic Minorities. 2010: Humana; Springer Science & Buisness Media.
In article      View Article
 
[22]  Ferdinand, K.C. and A.M. Armani, The management of hypertension in African Americans. Critical pathways in cardiology, 2007. 6(2): p. 67-71.
In article      View Article  PubMed
 
[23]  Diaz, K.M., et al., Prevalence, Determinants, and Clinical Significance of Masked Hypertension in a Population-Based Sample of African Americans: The Jackson Heart Study. Am J Hypertens, 2015. 28(7): p. 900-8.
In article      View Article  PubMed  PubMed
 
[24]  Patel, P.D., J.L. Velazquez, and R.R. Arora, Endothelial dysfunction in African-Americans. Int J Cardiol, 2009. 132(2): p. 157-72.
In article      View Article  PubMed
 
[25]  Veerabhadrappa, P., et al., Endothelial-dependent flow-mediated dilation in African Americans with masked-hypertension. Am J Hypertens, 2011. 24(10): p. 1102-7.
In article      View Article  PubMed  PubMed
 
[26]  Perticone, F., et al., Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation, 2001. 104(2): p. 191-6.
In article      View Article  PubMed
 
[27]  Cardillo, C. and J.A. Panza, Impaired endothelial regulation of vascular tone in patients with systemic arterial hypertension. Vasc Med, 1998. 3(2): p. 138-44.
In article      View Article  PubMed
 
[28]  Taddei, S., et al., Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation, 1996. 94(6): p. 1298-303.
In article      View Article  PubMed
 
[29]  Campia, U., et al., Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans. J Am Coll Cardiol, 2002. 40(4): p. 754-60.
In article      View Article
 
[30]  Perregaux, D., et al., Brachial vascular reactivity in blacks. Hypertension, 2000. 36(5): p. 866-71.
In article      View Article  PubMed
 
[31]  Cook, M.D., Endothelial Cell Function and Hypertension: Interactions Among Inflammation, Immune Function, and Exercise, in Effects of Exercise on Hypertension: From Cells to Physiological Systems, L.S. Pescatello, Editor. 2015, Humana Press: Springer: New York. p. 301-323.
In article      View Article
 
[32]  Babbitt, D.M., et al., Endothelial activation microparticles and inflammation status improve with exercise training in african americans. International journal of hypertension, 2013. 2013: p. 538017.
In article      View Article  PubMed  PubMed
 
[33]  Brown, M.D., et al., Racial differences in tumor necrosis factor-alpha-induced endothelial microparticles and interleukin-6 production. Vascular health and risk management, 2011. 7: p. 541-50.
In article      View Article  PubMed  PubMed
 
[34]  Diaz, K.M., et al., Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans. J Hum Hypertens, 2013. 27(11): p. 671-7.
In article      View Article  PubMed  PubMed
 
[35]  Feairheller, D.L., et al., Effects of moderate aerobic exercise training on vascular health and blood pressure in African Americans. J Clin Hypertens (Greenwich), 2014. 16(7): p. 504-10.
In article      View Article  PubMed  PubMed
 
[36]  Brown, M.D. and D.L. Feairheller, Are there race-dependent endothelial cell responses to exercise? Exerc Sport Sci Rev, 2013. 41(1): p. 44-54.
In article      View Article  PubMed  PubMed
 
[37]  Brown, M.D., et al., Racial differences in tumor necrosis factor-alpha-induced endothelial microparticles and interleukin-6 production. Vasc Health Risk Manag, 2011. 7: p. 541-50.
In article      View Article  PubMed  PubMed
 
[38]  Feairheller, D.L., et al., Racial differences in oxidative stress and inflammation: in vitro and in vivo. Clin Transl Sci, 2011. 4(1): p. 32-7.
In article      View Article  PubMed  PubMed
 
[39]  Lovren, F. and S. Verma, Evolving role of microparticles in the pathophysiology of endothelial dysfunction. Clin Chem, 2013. 59(8): p. 1166-74.
In article      View Article  PubMed
 
[40]  Spieker, L.E., et al., Working under pressure: the vascular endothelium in arterial hypertension. J Hum Hypertens, 2000. 14(10-11): p. 617-30.
In article      View Article  PubMed
 
[41]  Ekholm, M., et al., Effects of Angiotensin-Converting Enzyme Inhibition and Alpha 1-Adrenergic Receptor Blockade on Inflammation and Hemostasis in Human Hypertension. J Cardiovasc Pharmacol, 2018. 71(4): p. 240-247.
In article      View Article  PubMed
 
[42]  Lund, L.H., ACE inhibitors in African Americans with hypertension associated with worse outcomes as compared to other antihypertensives. Evid Based Med, 2016. 21(1): p. 33-4.
In article      View Article  PubMed
 
[43]  Grimm, H., et al., The Effects of Exercise, Aspirin, and Celecoxib in an Atherogenic Environment. Med Sci Sports Exerc, 2018. 50(10): p. 2033-2039.
In article      View Article  PubMed
 
[44]  Cheng, Y., et al., Role of prostacyclin in the cardiovascular response to thromboxane A2. Science, 2002. 296(5567): p. 539-41.
In article      View Article  PubMed
 
[45]  Cipollone, F., G. Cicolini, and M. Bucci, Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives. Pharmacol Ther, 2008. 118(2): p. 161-80.
In article      View Article  PubMed
 
[46]  Collado, M.C., et al., Gut microbiota: a source of novel tools to reduce the risk of human disease? Pediatr Res, 2015. 77(1-2): p. 182-8.
In article      View Article  PubMed
 
[47]  Sekirov, I., et al., Gut microbiota in health and disease. Physiol Rev, 2010. 90(3): p. 859-904.
In article      View Article  PubMed
 
[48]  Guo, Z., et al., Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis, 2011. 21(11): p. 844-50.
In article      View Article  PubMed
 
[49]  Tabuchi, M., et al., Antidiabetic effect of Lactobacillus GG in streptozotocin-induced diabetic rats. Biosci Biotechnol Biochem, 2003. 67(6): p. 1421-4.
In article      View Article  PubMed
 
[50]  Cole-Jeffrey, C.T., et al., ACE2 and Microbiota: Emerging Targets for Cardiopulmonary Disease Therapy. J Cardiovasc Pharmacol, 2015.
In article      View Article  PubMed  PubMed
 
[51]  Khalesi, S., et al., Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension, 2014. 64(4): p. 897-903.
In article      View Article  PubMed
 
[52]  Gomez-Guzman, M., et al., Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res, 2015.
In article      View Article  PubMed
 
[53]  Yang, T., et al., Gut dysbiosis is linked to hypertension. Hypertension, 2015. 65(6): p. 1331-40.
In article      View Article  PubMed  PubMed
 
[54]  Yan, Q., et al., Alterations of the Gut Microbiome in Hypertension. Front Cell Infect Microbiol, 2017. 7: p. 381.
In article      View Article  PubMed  PubMed
 
[55]  Hester, C.M., et al., Fecal microbes, short chain fatty acids, and colorectal cancer across racial/ethnic groups. World J Gastroenterol, 2015. 21(9): p. 2759-69.
In article      View Article  PubMed  PubMed
 
[56]  Ciubotaru, I., et al., Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans. Transl Res, 2015. 166(5): p. 401-11.
In article      View Article  PubMed  PubMed
 
[57]  Goodrich, J.K., et al., Human genetics shape the gut microbiome. Cell, 2014. 159(4): p. 789-99.
In article      View Article  PubMed  PubMed
 
[58]  Ou, J., et al., Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr, 2013. 98(1): p. 111-20.
In article      View Article  PubMed  PubMed
 
[59]  O'Keefe, S.J., Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol, 2016. 13(12): p. 691-706.
In article      View Article  PubMed  PubMed
 
[60]  Bailey, M.T., Psychological Stress, Immunity, and the Effects on Indigenous Microflora. Adv Exp Med Biol, 2016. 874: p. 225-46.
In article      
 
[61]  Serino, M., et al., Far from the eyes, close to the heart: dysbiosis of gut microbiota and cardiovascular consequences. Curr Cardiol Rep, 2014. 16(11): p. 540.
In article      View Article  PubMed  PubMed
 
[62]  Desai, M.S., et al., A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, 2016. 167(5): p. 1339-1353 e21.
In article      View Article  PubMed  PubMed
 
[63]  Santisteban, M.M., et al., Hypertension-Linked Pathophysiological Alterations in the Gut. Circ Res, 2016.
In article      
 
[64]  Li, J., et al., Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome, 2017. 5(1): p. 14.
In article      View Article  PubMed  PubMed
 
[65]  Podschun, R. and U. Ullmann, Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev, 1998. 11(4): p. 589-603.
In article      View Article  PubMed  PubMed
 
[66]  Ley, R.E., Gut microbiota in 2015: Prevotella in the gut: choose carefully. Nat Rev Gastroenterol Hepatol, 2016. 13(2): p. 69-70.
In article      View Article  PubMed
 
[67]  Kumar, S., et al., Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells. Biochemistry, 2005. 44(48): p. 15944-52.
In article      View Article  PubMed
 
[68]  Chamkha, M., J.L. Garcia, and M. Labat, Metabolism of cinnamic acids by some Clostridiales and emendation of the descriptions of Clostridium aerotolerans, Clostridium celerecrescens and Clostridium xylanolyticum. Int J Syst Evol Microbiol, 2001. 51(Pt 6): p. 2105-11.
In article      View Article  PubMed
 
[69]  Morrison, D.J. and T. Preston, Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes, 2016. 7(3): p. 189-200.
In article      View Article  PubMed  PubMed
 
[70]  Pevsner-Fischer, M., et al., The gut microbiome and hypertension. Curr Opin Nephrol Hypertens, 2017. 26(1): p. 1-8.
In article      View Article  PubMed
 
[71]  Wong, J.M., et al., Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol, 2006. 40(3): p. 235-43.
In article      View Article  PubMed
 
[72]  O'Keefe, S.J., et al., Why do African Americans get more colon cancer than Native Africans? J Nutr, 2007. 137(1 Suppl): p. 175S-182S.
In article      View Article  PubMed
 
[73]  Pluznick, J., A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes, 2014. 5(2): p. 202-7.
In article      View Article  PubMed  PubMed
 
[74]  Zapolska-Downar, D., et al., Butyrate inhibits cytokine-induced VCAM-1 and ICAM-1 expression in cultured endothelial cells: the role of NF-kappaB and PPARalpha. J Nutr Biochem, 2004. 15(4): p. 220-8.
In article      View Article  PubMed
 
[75]  van der Beek, C.M., et al., Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans. J Nutr, 2015. 145(9): p. 2019-24.
In article      View Article  PubMed
 
[76]  Wilck, N., et al., Salt-responsive gut commensal modulates TH17 axis and disease. Nature, 2017. 551(7682): p. 585-589.
In article      View Article  PubMed  PubMed
 
[77]  LeBlanc, J.G., et al., Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact, 2017. 16(1): p. 79.
In article      View Article  PubMed  PubMed
 
[78]  Cook, M.D., et al., Exercise and gut immune function: Evidence of alterations in colon immune cell homeostasis and microbiome characteristics with exercise training. Immunol Cell Biol, 2015.
In article      View Article  PubMed
 
[79]  Allen, J.M., et al., Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med Sci Sports Exerc, 2017.
In article      
 
[80]  Mailing, L.J., et al., Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health. Exerc Sport Sci Rev, 2019. 47(2): p. 75-85.
In article      View Article  PubMed
 
[81]  Brown, M.D. and D.L. Feairheller, Are there race-dependent endothelial cell responses to exercise? Exercise and sport sciences reviews, 2013. 41(1): p. 44-54.
In article      View Article  PubMed  PubMed
 
[82]  Gleeson, M., et al., The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews. Immunology, 2011. 11(9): p. 607-15.
In article      View Article  PubMed
 
[83]  Wilson, I.D. and J.K. Nicholson, Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res, 2017. 179: p. 204-222.
In article      View Article  PubMed  PubMed
 

Published with license by Science and Education Publishing, Copyright © 2019 Marc D. Cook, Lanna Anderson, Maitha Aldokhayyil, Adelola Adeyemo, Mesha Guinyard and Michael Brown

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Cite this article:

Normal Style
Marc D. Cook, Lanna Anderson, Maitha Aldokhayyil, Adelola Adeyemo, Mesha Guinyard, Michael Brown. Endothelial Dysfunction and Hypertension in African Americans: Overview of the Role of the Gut Microbiome. American Journal of Hypertension Research. Vol. 6, No. 1, 2019, pp 1-7. http://pubs.sciepub.com/ajhr/6/1/1
MLA Style
Cook, Marc D., et al. "Endothelial Dysfunction and Hypertension in African Americans: Overview of the Role of the Gut Microbiome." American Journal of Hypertension Research 6.1 (2019): 1-7.
APA Style
Cook, M. D. , Anderson, L. , Aldokhayyil, M. , Adeyemo, A. , Guinyard, M. , & Brown, M. (2019). Endothelial Dysfunction and Hypertension in African Americans: Overview of the Role of the Gut Microbiome. American Journal of Hypertension Research, 6(1), 1-7.
Chicago Style
Cook, Marc D., Lanna Anderson, Maitha Aldokhayyil, Adelola Adeyemo, Mesha Guinyard, and Michael Brown. "Endothelial Dysfunction and Hypertension in African Americans: Overview of the Role of the Gut Microbiome." American Journal of Hypertension Research 6, no. 1 (2019): 1-7.
Share
[1]  Kjeldsen, S.E., Hypertension and cardiovascular risk: General aspects. Pharmacol Res, 2018. 129: p. 95-99.
In article      View Article  PubMed
 
[2]  Dad, T. and D.E. Weiner, Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages. Semin Nephrol, 2015. 35(4): p. 311-22.
In article      View Article  PubMed  PubMed
 
[3]  Lawes, C.M., et al., Blood pressure and stroke: an overview of published reviews. Stroke, 2004. 35(4): p. 1024.
In article      View Article  PubMed
 
[4]  System, U.S.R.D., Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, in USRDS Annual Data Report. 2009, National Institute of Diabetes and Digestive and Kidney Disease.
In article      
 
[5]  Murray, C.J., et al., The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA, 2013. 310(6): p. 591-608.
In article      View Article  PubMed  PubMed
 
[6]  Mills, K.T., et al., Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation, 2016. 134(6): p. 441-50.
In article      View Article  PubMed  PubMed
 
[7]  Egan, B.M., et al., Hypertension in the United States, 1999 to 2012: progress toward Healthy People 2020 goals. Circulation, 2014. 130(19): p. 1692-9.
In article      View Article  PubMed  PubMed
 
[8]  Fryar, C.D., et al., Hypertension Prevalence and Control Among Adults: United States, 2015-2016. NCHS Data Brief, 2017(289): p. 1-8.
In article      
 
[9]  Egan, B.M., Y. Zhao, and R.N. Axon, US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA, 2010. 303(20): p. 2043-50.
In article      View Article  PubMed
 
[10]  Heidenreich, P.A., et al., Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation, 2011. 123(8): p. 933-44.
In article      View Article  PubMed
 
[11]  Kirkland, E.B., et al., Trends in Healthcare Expenditures Among US Adults With Hypertension: National Estimates, 2003-2014. J Am Heart Assoc, 2018. 7(11).
In article      View Article  PubMed  PubMed
 
[12]  Carnethon, M.R., et al., Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association. Circulation, 2017. 136(21): p. e393-e423.
In article      View Article  PubMed
 
[13]  Ferdinand, K.C. and R.R. Townsend, Hypertension in the US Black population: risk factors, complications, and potential impact of central aortic pressure on effective treatment. Cardiovasc Drugs Ther, 2012. 26(2): p. 157-65.
In article      View Article  PubMed
 
[14]  Muntner, P., et al., Trends in blood pressure among children and adolescents. JAMA, 2004. 291(17): p. 2107-13.
In article      View Article  PubMed
 
[15]  Kalinowski, L., I.T. Dobrucki, and T. Malinski, Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases. Circulation, 2004. 109(21): p. 2511-7.
In article      View Article  PubMed
 
[16]  Hozawa, A., et al., Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects--Atherosclerosis Risk in Communities Study. Archives of internal medicine, 2007. 167(6): p. 573-9.
In article      View Article  PubMed
 
[17]  Benjamin, E.J., et al., Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, 2019. 139(10): p. e56-e528.
In article      
 
[18]  Go, A.S., et al., Heart disease and stroke statistics--2014 update: a report from the american heart association. Circulation, 2014. 129(3): p. e28-e292.
In article      
 
[19]  Egan, B.M., et al., Hypertension in the United States 1999–2012: Progress Toward Healthy People 2020 Goals. Circulation, 2014. 130(19): p. 1692-9.
In article      View Article  PubMed  PubMed
 
[20]  Thorpe, R.J., et al., Economic Burden of Men's Health Disparities in the United States. International Journal of Men's Health, 2013. 12(3).
In article      View Article
 
[21]  Ferdinand, K.C. and A. Armani, Cardiovascular Disease in Racial and Ethnic Minorities. 2010: Humana; Springer Science & Buisness Media.
In article      View Article
 
[22]  Ferdinand, K.C. and A.M. Armani, The management of hypertension in African Americans. Critical pathways in cardiology, 2007. 6(2): p. 67-71.
In article      View Article  PubMed
 
[23]  Diaz, K.M., et al., Prevalence, Determinants, and Clinical Significance of Masked Hypertension in a Population-Based Sample of African Americans: The Jackson Heart Study. Am J Hypertens, 2015. 28(7): p. 900-8.
In article      View Article  PubMed  PubMed
 
[24]  Patel, P.D., J.L. Velazquez, and R.R. Arora, Endothelial dysfunction in African-Americans. Int J Cardiol, 2009. 132(2): p. 157-72.
In article      View Article  PubMed
 
[25]  Veerabhadrappa, P., et al., Endothelial-dependent flow-mediated dilation in African Americans with masked-hypertension. Am J Hypertens, 2011. 24(10): p. 1102-7.
In article      View Article  PubMed  PubMed
 
[26]  Perticone, F., et al., Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation, 2001. 104(2): p. 191-6.
In article      View Article  PubMed
 
[27]  Cardillo, C. and J.A. Panza, Impaired endothelial regulation of vascular tone in patients with systemic arterial hypertension. Vasc Med, 1998. 3(2): p. 138-44.
In article      View Article  PubMed
 
[28]  Taddei, S., et al., Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation, 1996. 94(6): p. 1298-303.
In article      View Article  PubMed
 
[29]  Campia, U., et al., Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans. J Am Coll Cardiol, 2002. 40(4): p. 754-60.
In article      View Article
 
[30]  Perregaux, D., et al., Brachial vascular reactivity in blacks. Hypertension, 2000. 36(5): p. 866-71.
In article      View Article  PubMed
 
[31]  Cook, M.D., Endothelial Cell Function and Hypertension: Interactions Among Inflammation, Immune Function, and Exercise, in Effects of Exercise on Hypertension: From Cells to Physiological Systems, L.S. Pescatello, Editor. 2015, Humana Press: Springer: New York. p. 301-323.
In article      View Article
 
[32]  Babbitt, D.M., et al., Endothelial activation microparticles and inflammation status improve with exercise training in african americans. International journal of hypertension, 2013. 2013: p. 538017.
In article      View Article  PubMed  PubMed
 
[33]  Brown, M.D., et al., Racial differences in tumor necrosis factor-alpha-induced endothelial microparticles and interleukin-6 production. Vascular health and risk management, 2011. 7: p. 541-50.
In article      View Article  PubMed  PubMed
 
[34]  Diaz, K.M., et al., Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans. J Hum Hypertens, 2013. 27(11): p. 671-7.
In article      View Article  PubMed  PubMed
 
[35]  Feairheller, D.L., et al., Effects of moderate aerobic exercise training on vascular health and blood pressure in African Americans. J Clin Hypertens (Greenwich), 2014. 16(7): p. 504-10.
In article      View Article  PubMed  PubMed
 
[36]  Brown, M.D. and D.L. Feairheller, Are there race-dependent endothelial cell responses to exercise? Exerc Sport Sci Rev, 2013. 41(1): p. 44-54.
In article      View Article  PubMed  PubMed
 
[37]  Brown, M.D., et al., Racial differences in tumor necrosis factor-alpha-induced endothelial microparticles and interleukin-6 production. Vasc Health Risk Manag, 2011. 7: p. 541-50.
In article      View Article  PubMed  PubMed
 
[38]  Feairheller, D.L., et al., Racial differences in oxidative stress and inflammation: in vitro and in vivo. Clin Transl Sci, 2011. 4(1): p. 32-7.
In article      View Article  PubMed  PubMed
 
[39]  Lovren, F. and S. Verma, Evolving role of microparticles in the pathophysiology of endothelial dysfunction. Clin Chem, 2013. 59(8): p. 1166-74.
In article      View Article  PubMed
 
[40]  Spieker, L.E., et al., Working under pressure: the vascular endothelium in arterial hypertension. J Hum Hypertens, 2000. 14(10-11): p. 617-30.
In article      View Article  PubMed
 
[41]  Ekholm, M., et al., Effects of Angiotensin-Converting Enzyme Inhibition and Alpha 1-Adrenergic Receptor Blockade on Inflammation and Hemostasis in Human Hypertension. J Cardiovasc Pharmacol, 2018. 71(4): p. 240-247.
In article      View Article  PubMed
 
[42]  Lund, L.H., ACE inhibitors in African Americans with hypertension associated with worse outcomes as compared to other antihypertensives. Evid Based Med, 2016. 21(1): p. 33-4.
In article      View Article  PubMed
 
[43]  Grimm, H., et al., The Effects of Exercise, Aspirin, and Celecoxib in an Atherogenic Environment. Med Sci Sports Exerc, 2018. 50(10): p. 2033-2039.
In article      View Article  PubMed
 
[44]  Cheng, Y., et al., Role of prostacyclin in the cardiovascular response to thromboxane A2. Science, 2002. 296(5567): p. 539-41.
In article      View Article  PubMed
 
[45]  Cipollone, F., G. Cicolini, and M. Bucci, Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives. Pharmacol Ther, 2008. 118(2): p. 161-80.
In article      View Article  PubMed
 
[46]  Collado, M.C., et al., Gut microbiota: a source of novel tools to reduce the risk of human disease? Pediatr Res, 2015. 77(1-2): p. 182-8.
In article      View Article  PubMed
 
[47]  Sekirov, I., et al., Gut microbiota in health and disease. Physiol Rev, 2010. 90(3): p. 859-904.
In article      View Article  PubMed
 
[48]  Guo, Z., et al., Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis, 2011. 21(11): p. 844-50.
In article      View Article  PubMed
 
[49]  Tabuchi, M., et al., Antidiabetic effect of Lactobacillus GG in streptozotocin-induced diabetic rats. Biosci Biotechnol Biochem, 2003. 67(6): p. 1421-4.
In article      View Article  PubMed
 
[50]  Cole-Jeffrey, C.T., et al., ACE2 and Microbiota: Emerging Targets for Cardiopulmonary Disease Therapy. J Cardiovasc Pharmacol, 2015.
In article      View Article  PubMed  PubMed
 
[51]  Khalesi, S., et al., Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension, 2014. 64(4): p. 897-903.
In article      View Article  PubMed
 
[52]  Gomez-Guzman, M., et al., Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res, 2015.
In article      View Article  PubMed
 
[53]  Yang, T., et al., Gut dysbiosis is linked to hypertension. Hypertension, 2015. 65(6): p. 1331-40.
In article      View Article  PubMed  PubMed
 
[54]  Yan, Q., et al., Alterations of the Gut Microbiome in Hypertension. Front Cell Infect Microbiol, 2017. 7: p. 381.
In article      View Article  PubMed  PubMed
 
[55]  Hester, C.M., et al., Fecal microbes, short chain fatty acids, and colorectal cancer across racial/ethnic groups. World J Gastroenterol, 2015. 21(9): p. 2759-69.
In article      View Article  PubMed  PubMed
 
[56]  Ciubotaru, I., et al., Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans. Transl Res, 2015. 166(5): p. 401-11.
In article      View Article  PubMed  PubMed
 
[57]  Goodrich, J.K., et al., Human genetics shape the gut microbiome. Cell, 2014. 159(4): p. 789-99.
In article      View Article  PubMed  PubMed
 
[58]  Ou, J., et al., Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr, 2013. 98(1): p. 111-20.
In article      View Article  PubMed  PubMed
 
[59]  O'Keefe, S.J., Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol, 2016. 13(12): p. 691-706.
In article      View Article  PubMed  PubMed
 
[60]  Bailey, M.T., Psychological Stress, Immunity, and the Effects on Indigenous Microflora. Adv Exp Med Biol, 2016. 874: p. 225-46.
In article      
 
[61]  Serino, M., et al., Far from the eyes, close to the heart: dysbiosis of gut microbiota and cardiovascular consequences. Curr Cardiol Rep, 2014. 16(11): p. 540.
In article      View Article  PubMed  PubMed
 
[62]  Desai, M.S., et al., A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, 2016. 167(5): p. 1339-1353 e21.
In article      View Article  PubMed  PubMed
 
[63]  Santisteban, M.M., et al., Hypertension-Linked Pathophysiological Alterations in the Gut. Circ Res, 2016.
In article      
 
[64]  Li, J., et al., Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome, 2017. 5(1): p. 14.
In article      View Article  PubMed  PubMed
 
[65]  Podschun, R. and U. Ullmann, Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev, 1998. 11(4): p. 589-603.
In article      View Article  PubMed  PubMed
 
[66]  Ley, R.E., Gut microbiota in 2015: Prevotella in the gut: choose carefully. Nat Rev Gastroenterol Hepatol, 2016. 13(2): p. 69-70.
In article      View Article  PubMed
 
[67]  Kumar, S., et al., Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells. Biochemistry, 2005. 44(48): p. 15944-52.
In article      View Article  PubMed
 
[68]  Chamkha, M., J.L. Garcia, and M. Labat, Metabolism of cinnamic acids by some Clostridiales and emendation of the descriptions of Clostridium aerotolerans, Clostridium celerecrescens and Clostridium xylanolyticum. Int J Syst Evol Microbiol, 2001. 51(Pt 6): p. 2105-11.
In article      View Article  PubMed
 
[69]  Morrison, D.J. and T. Preston, Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes, 2016. 7(3): p. 189-200.
In article      View Article  PubMed  PubMed
 
[70]  Pevsner-Fischer, M., et al., The gut microbiome and hypertension. Curr Opin Nephrol Hypertens, 2017. 26(1): p. 1-8.
In article      View Article  PubMed
 
[71]  Wong, J.M., et al., Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol, 2006. 40(3): p. 235-43.
In article      View Article  PubMed
 
[72]  O'Keefe, S.J., et al., Why do African Americans get more colon cancer than Native Africans? J Nutr, 2007. 137(1 Suppl): p. 175S-182S.
In article      View Article  PubMed
 
[73]  Pluznick, J., A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes, 2014. 5(2): p. 202-7.
In article      View Article  PubMed  PubMed
 
[74]  Zapolska-Downar, D., et al., Butyrate inhibits cytokine-induced VCAM-1 and ICAM-1 expression in cultured endothelial cells: the role of NF-kappaB and PPARalpha. J Nutr Biochem, 2004. 15(4): p. 220-8.
In article      View Article  PubMed
 
[75]  van der Beek, C.M., et al., Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans. J Nutr, 2015. 145(9): p. 2019-24.
In article      View Article  PubMed
 
[76]  Wilck, N., et al., Salt-responsive gut commensal modulates TH17 axis and disease. Nature, 2017. 551(7682): p. 585-589.
In article      View Article  PubMed  PubMed
 
[77]  LeBlanc, J.G., et al., Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact, 2017. 16(1): p. 79.
In article      View Article  PubMed  PubMed
 
[78]  Cook, M.D., et al., Exercise and gut immune function: Evidence of alterations in colon immune cell homeostasis and microbiome characteristics with exercise training. Immunol Cell Biol, 2015.
In article      View Article  PubMed
 
[79]  Allen, J.M., et al., Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med Sci Sports Exerc, 2017.
In article      
 
[80]  Mailing, L.J., et al., Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health. Exerc Sport Sci Rev, 2019. 47(2): p. 75-85.
In article      View Article  PubMed
 
[81]  Brown, M.D. and D.L. Feairheller, Are there race-dependent endothelial cell responses to exercise? Exercise and sport sciences reviews, 2013. 41(1): p. 44-54.
In article      View Article  PubMed  PubMed
 
[82]  Gleeson, M., et al., The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews. Immunology, 2011. 11(9): p. 607-15.
In article      View Article  PubMed
 
[83]  Wilson, I.D. and J.K. Nicholson, Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res, 2017. 179: p. 204-222.
In article      View Article  PubMed  PubMed