Hypertension-Linked Pathophysiological Alterations in the Gut

Santisteban, Monica M; Qi, Yan; Zubcevic, Jasenka; Kim, Seungbum; Yang, Tao; Shenoy, Vinayak; Cole‐Jeffrey, Colleen T.; Lobaton, Gilberto O; Stewart, Daniel; Rubiano, Andrés M.; Simmons, Chelsey S.; Garcia‐Pereira, Fernando; Johnson, Richard D.; Pepine, Carl J.; Raizada, Mohan K.

doi:10.1161/circresaha.116.309006

Cited by 409 publications

(500 citation statements)

References 55 publications

Supporting

Mentioning

465

Contrasting

Unclassified

Order By: Relevance

“…Changes in microbiota have been associated with alterations in gut pathology in animal models of HTN [12]. However, little is known about gut microbiota and its relationship with gut barrier function in patients with HBP.…”

Section: Discussionmentioning

confidence: 99%

“…Our results demonstrate a strong correlation of SBP with gut bacteria and barrier dysfunction, which may provide important clues to the role of microbiome in HTN. We have previously shown that increased gut sympathetic nerve activity and reduced gut tight junction proteins precede development of HTN in spontaneously hypertensive rats [12]. Together, it is tempting to speculate that prohypertensive signals (diet, salt, environment, toxins etc.)…”

Section: Discussionmentioning

confidence: 99%

“…While roles of the brain, kidney, bone marrow, and immune cells in BP regulation have been thoroughly investigated, involvement of the gut, one of the largest endocrine, immune, and neural organs in the body [6,7], in HTN has been underestimated. There are multiple reasons to investigate gut and its microbiome in HTN; (i) gut is the single most important organ for adsorption of nutrients and ions, which impacts BP greatly [8–10], (ii) dysregulation of microbiota is related to various metabolic diseases and HTN risk factors such as obesity, heart failure, and diabetes mellitus [11], indicating a major role in BP regulation, (iii) gut pathophysiology in animal HTN models [12], and (iv) fecal transplantation from HTN subjects can elevate BP of normal animals [13,14]. These observations suggest the gut as a promising new therapeutic target for human HTN.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…With aging of the intestinal epithelium, ischemic changes, low-grade inflammation and the increased use of nonsteroidal anti-inflammatory drugs hamper the normal function and regenerative capacity of the epithelial barrier which can lead to a mucosal injury [26] [42]. In addition, hypertension has been proposed to induce a low-grade inflammation in the gut epithelium [43]. We hypothesized that inflammatory changes could be balanced with increased corticosterone production, but no correlation was found between these two variables.…”

Section: Discussionmentioning

confidence: 99%

Local Intestinal ACE-Like Activity and Corticosterone Production in Hypertensive and Aging Rats

Salmenkari¹,

Holappa²,

Siltari³

et al. 2018

View full text Add to dashboard Cite

The renin angiotensin system (RAS) participates in inflammatory processes, as either a pro-inflammatory or an anti-inflammatory mediator. Components of RAS, such as angiotensin-converting enzyme (ACE), have been detected locally in the gut epithelium. In addition, the anti-inflammatory steroid, corticosterone, is produced in the gut. Hypertension and aging evoke a low-grade inflammatory process in the vascular endothelium. It is not known whether they induce a similar low-grade inflammation in the intestine and if the low-grade inflammation would evoke an activation of ACE and an elevation of corticosterone production. These two variables were measured in ileum and colon of 9-and 26-week old spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WK) controls. ACE-activity, measured via the formation of histidyl-leucine from hippuryl-histidyl-leucine in the tissue homogenate samples, was similar in the ileum and colon of young animals although the ileum of the young normotensive animals displayed the lowest level. In the old animals, the ACE activity was higher in the ileum than in the colon, especially in normotensive rats. Corticosterone production was measured as corticosterone concentration in the supernatants of ileum or colon after a 90-min ex vivo incubation. Corticosterone production was higher in ileum than in colon in both SHR and WK. No clear evidence was seen for age-dependency or for an effect of hypertension in the measured variables in the intestine. Thus, the putative low-grade inflammation in the intestine in aging or hypertension is not a strong enough stimulus to elevate corticosterone production or activate ACE.

show abstract

“…Gut receives significant sympathetic innervation. Monica M et al [32] demonstrated that in hypertension, the gut changed pathologically and associated with alterations in microbial communities. The dysfunction of sympathetic-gut communication is associated with gut pathology, dysbiosis and inflammation, last but not least, relevant to hypertension.…”

Section: Animal Modelmentioning

confidence: 99%

Gut Microbiota, a Rising Star in Hypertension

Hui¹

2017

MOJAP

View full text Add to dashboard Cite

Submit Manuscript | http://medcraveonline.com enormous burden on society and a low-level quality of lifestyle on the patient. The overall prevalence of hypertension has not changed since [2009][2010], the young adults still have lower awareness of their hypertension and 75 percent people taken medicine to lower hypertension [1]. Hypertension may be either primary or secondary. For primary hypertension, 95% of all hypertensive cases was diagnosed with no known cause [2], the known etiological factor is salt intake, obesity, insulin resistance, aging and perhaps sedentary lifestyle, stress, inherited BP [3]. The regular therapy of hypertension control is the anti-hypertension drugs which often have the poor medication adherence and complications. As for white-coat hypertension, H-type hypertension, and resistant hypertension, the treatment is still intractable. Thus, diet modification or identifying new therapeutic targets that produce reductions in hypertrophy has considerable importance for public health. Gut microbiota, a forgotten organ in our organisms, its whole role was rarely reported and attracted attention in hypertension previously. The Microbiota in Human Intestinal TractIt is estimated that a number of the human microbiota is ten times higher than that human cells [4]. And our intestinal tract is a nutrient-rich environment, containing huge numbers of microorganisms, up to 100 trillion, often called gut microbiota [5]. The human intestinal microbiota is primarily dominated by the Bacteroidetes and the Firmicutes; other microbiota is present in the minor properties [6]. Paul B. Eckburg et al. [6] improved understanding of gut microbial diversity and discovered that significant intersubject variability and differences between mucosa community composition and stool through the examining 13355 prokaryotic ribosomal RNA (rRNA) gene sequences from multiple colonic mucosal sites and feces of healthy subjects. Bing Han et al. [7] have found that certain bacterial mutants promote host longevity and developing genetically engineered probiotics hold great promise for promoting healthy aging and as a new therapeutic paradigm. Factors that Regulate MicrobiotaMany factors could regulate microbiota, among them, the environmental factor, host genotype, age, health status, diet and so on are in hot discussion and research. Host genetic and multiple environmental control is in shaping individuality in gut microbiota composition, which is often a complex polygenic trait [8]. Marcus J Claesson et al. [9] demonstrate that gut microbiota composition strongly associated with diet and health in the elderly. They found that the microbiota composition was less diverse in the individual who was in long-stay care and significantly associated with the frailty, co-morbidity, nutritional status and so on. Exercise, an important role in host metabolism and immunity, is also a beneficial impact on microbiota diversity [10]. With the complete of gene pool, 16S rRNA sequencing technology has been one of the forceful facilities for the ...

show abstract

Hypertension-Linked Pathophysiological Alterations in the Gut

Cited by 409 publications

References 55 publications

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Local Intestinal ACE-Like Activity and Corticosterone Production in Hypertensive and Aging Rats

Gut Microbiota, a Rising Star in Hypertension

Contact Info

Product

Resources

About