The Gut, Its Microbiome, and Hypertension

Richards, Elaine M.; Pepine, Carl J.; Raizada, Mohan K.; Kim, Seungbum

doi:10.1007/s11906-017-0734-1

Cited by 114 publications

(67 citation statements)

References 76 publications

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“…The small intestine is the most abundant source of ACE2 and has been linked with regulation of antimicrobial peptides and microbiota (4,11). Our studies have shown profound differences in gut microbiota in ACE2 knockin mice (12). Because the gut is the biggest immune organ and is highly innervated, it is reasonable to infer that gut ACE2-mediated effects on immune and neural systems might impact pulmonary functions.…”

Section: Supported By Nih Grant R01-hl102033mentioning

confidence: 72%

ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?

Richards

Raizada

2018

Am J Respir Crit Care Med

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Section: Supported By Nih Grant R01-hl102033mentioning

confidence: 72%

ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?

Richards

Raizada

2018

Am J Respir Crit Care Med

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“…Evidence has been accumulating in recent years emphasizing the involvement of gut microbiota in HTN [56,57]. Changes in microbiota have been associated with alterations in gut pathology in animal models of HTN [12].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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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“…Changes in gut microbiota composition are associated with aging (14), with indices of age-related inflammation (14,15), and with a higher risk of inflammatory bowel disease and irritable bowel syndrome (16). In addition, other extra-gastrointestinal diseases such as atherosclerosis, metabolic syndrome, hypertension, type 2 diabetes, and neuromusculoskeletal diseases (i.e., cachexia and frailty) are also associated with gut dysbiosis (3,11,(17)(18)(19)(20)(21). Imbalance of the gut microbiome is also associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease (22)(23)(24)(25) and multiple sclerosis (26,27) (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

et al. 2020

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Cognitive frailty is a geriatric condition defined by the coexistence of cognitive impairment and physical frailty. This "composite" aging phenotype is associated with a higher risk of several adverse health-related outcomes, including dementia. In the last decade, cognitive frailty has gained increased attention from the scientific community that has focused on understanding the clinical impact and the physiological and pathological mechanisms of development and on identifying preventive and/or rehabilitative therapeutic interventions. The emergence of gut microbiome in neural signaling increased the interest in targeting the gut-brain axis as a modulation strategy. Multiple studies on gastroenteric, metabolic, and neurodegenerative diseases support the existence of a wide bidirectional communication network of signaling mediators, e.g., bioactive lipids, that can modulate inflammation, gut permeability, microbiota composition, and the gut-brain axis. This crosstalk between the gut-brain axis, microbiome, and bioactive lipids may emerge as the basis of a promising therapeutic strategy to counteract cognitive frailty. In this review, we summarize the evidence in the literature regarding the link between the gut microbiome, brain, and several families of bioactive lipids. In addition, we also explore the applicability of several bioactive lipid members as a potential routes for therapeutic interventions to combat cognitive frailty.

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The Gut, Its Microbiome, and Hypertension

Cited by 114 publications

References 76 publications

ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?

ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?

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

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

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