Gut microbiota dysbiosis contributes to the development of hypertension

Li, Jingjing; Zhao, Fangqing; Wang, Yidan; Chen, Junru; Tao, Jie; Tian, Gang; Wu, Shouling; Liu, Wenbin; Cui, Qinghua; Geng, Bin; Zhang, Weili; Weldon, Ryan; Auguste, Kelda; Yang, Lei; Liu, Xiaoyan; Chen, Li; Yang, Xinchun; Zhu, Baoli; Cai, Jun

doi:10.1186/s40168-016-0222-x

Cited by 1,276 publications

(1,385 citation statements)

References 66 publications

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“…Hypertension is a major cardiovascular risk factor arising from a complex interplay of both genetic and environmental factors [90]. Germ-free mice that lack intestinal bacteria have relatively lower blood pressure when compared with conventional mice [91] and fecal transplantation from hypertensive human donors to germ-free mice elevates blood pressure in these animals [90], suggesting that the gut flora influences blood pressure.…”

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 99%

“…Germ-free mice that lack intestinal bacteria have relatively lower blood pressure when compared with conventional mice [91] and fecal transplantation from hypertensive human donors to germ-free mice elevates blood pressure in these animals [90], suggesting that the gut flora influences blood pressure. In addition, rat studies and randomized clinical trials suggest that administration of probiotics can reduce blood pressure [92,93].…”

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 99%

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Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

et al. 2018

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In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease. Higher blood levels of gut-derived uremic toxins are associated with increased cardiovascular events and mortality in the CKD population. Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.

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Section: Cardiovascular Disease and Mortalitymentioning

confidence: 99%

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 99%

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

et al. 2018

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“…LPS is translocated to human circulation with chylomicrons and, therefore, increases after a meal, particularly in the case of a fatty meal, suggesting a prominent role of diet in modulating circulating LPS 9, 10. In addition, in some clinical settings such as hypertension, LPS may enter the systemic circulation as a consequence of increased gut permeability due to an impairment of tight junctions 11, 12. Experimental studies have showed that LPS is proatherogenic in vivo as its injection in mice and rabbits accelerates the formation of plaque 13.…”

Section: Introductionmentioning

confidence: 99%

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Pastori

Carnevale

Nocella

et al. 2017

JAHA

141

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BackgroundGut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet).Methods and ResultsThis was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log‐rank test P=0.004). Log‐LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P<0.001), and previous cerebrovascular (hazard ratio 1.634, P=0.004) and cardiac events (hazard ratio 1.822, P<0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (β 0.087, P=0.014) and low‐density lipoprotein cholesterol (β 0.069, P=0.049) were associated with circulating LPS. Furthermore, Med‐diet score (β −0.137, P<0.001) was predictive of log‐LPS, with fruits (β −0.083, P=0.030) and legumes (β −0.120, P=0.002) negatively associated with log‐LPS levels. Log‐LPS and log‐TxB2 were highly correlated (r=0.598, P<0.001). Log‐LPS (β 0.574, P<0.001) and Med‐diet score (β −0.218, P<0.001) were significantly associated with baseline urinary excretion of TxB2.ConclusionsIn this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med‐diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

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“…Hypertension is another major risk factor for the development of CVD. Experiments with germ-free mouse models have causally linked the gut microbiota and dysbiosis with the development of hypertension and vascular dysfunction [65,66]. In a study with 41 healthy controls, 56 pre-hypertensive subjects, and 99 individuals with primary hypertension, decreased microbial richness and diversity was revealed [66].…”

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confidence: 99%

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

2018

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Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury. Depending on nutritional factors, the microbiota-derived choline-metabolite trimethylamine Noxide (TMAO) increases atherosclerotic plaque size, triggers prothrombotic platelet function and promotes arterial thrombus growth. Hence, the composition of the commensal microbiota is an emerging risk factor for CVD. Here, we provide an overview on microbiota-dependent pathomechanisms that drive the development of CVD and arterial thrombosis.Keywords: Arterial thrombosis r Atherosclerosis r Cardiovascular disease r Microbiota r Toll-like receptors IntroductionAt birth, our body surfaces are colonized by microbial communities (microbiota), representing one of the most densely colonized microbial ecosystems [1]. This process is strongly influenced by genetic, nutritional, and environmental factors [2]. The commensal microbiota constitutes a permanent inflammatory stimulus [3], which is kept in check by the host's immune responses [4]. The microbiota can be viewed as an organ that impacts host physiology [5,6]. Changes in gut microbiota composition were associated with intestinal diseases (e.g. inflammatory bowel disease, colon cancer) and cardiometabolic disease states, such as diet-induced obesity, type 2 diabetes, atherosclerosis, and arterial thrombosis [7]. The results from recent experimental and clinical studies have led to the assumption that Correspondence: Christoph Reinhardt e-mail: Christoph.Reinhardt@unimedizin-mainz.de molecules synthesized by the intestinal microbiota are involved in the development of cardiovascular disease (CVD) [8] and may increase the risk of arterial thrombosis [9, 10] as well as the outcome of ischemic stroke [11]. Experimental evidence from germ-free mouse studies and metagenomics analyses have associated the gut microbiota with obesity [12][13][14][15], type 2 diabetes [3, 16, 17], stroke [11, 18], and CVD [8, 9, 19]. Therefore, targeting the composition and metabolic function of the intestinal microbiota may represent a therapeutic option that in the future may allow prevention and treatment of cardiometabolic diseases [20].Here, we provide a comprehensive overview on the emerging link between gut microbiota and CVD. We delineate the contribution of this complex microbial ecosystem to metabolic inflammation and its impact on host metabolism. The main focus of this review is to highlight how gut microbiota may contribute to the development of CVD, cerebrovascular disease and arterial thromb...

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Gut microbiota dysbiosis contributes to the development of hypertension

Cited by 1,276 publications

References 66 publications

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

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