Evidence for a link between gut microbiota and hypertension in the Dahl rat

Mell, Blair; Jala, Venkatakrishna R.; Mathew, Anna V.; Byun, Jaeman; Waghulde, Harshal; Zhang, Youjie; Haribabu, Bodduluri; Vijay‐Kumar, Matam; Pennathur, Subramaniam; Joe, Bina

doi:10.1152/physiolgenomics.00136.2014

Cited by 313 publications

(306 citation statements)

References 58 publications

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“…These two families contain bacteria associated with butyrate-production and are found in low-abundance in sedentary women, hypertensive Dahl salt-sensitive rats, and HFD mice fecal microbiota. 30 , 139 , 140 …”

Section: Discussionmentioning

confidence: 99%

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Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.

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Section: Discussionmentioning

confidence: 99%

“…Interestingly, studies of microbial transplantation have demonstrated that the microbiome affects blood pressure. 30 …”

Section: Introductionmentioning

confidence: 99%

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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“…78 A link between microbial content and BP regulation was also found in Dahl S and R rats. 79 The cross-talk between the gut microbiota and the renal and cardiovascular systems could be relevant to the pathogenesis and treatment of hypertension. An interesting and unanswered question is whether salt intake influences the microbiome and the gut-derived IL-17 response enhancing the development of arterial hypertension.…”

Section: Microbiomementioning

confidence: 99%

Immune Mechanisms in Arterial Hypertension

Wenzel¹,

Turner²,

Krebs³

et al. 2016

Journal of the American Society of Nephrology

165

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Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive endorgan damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

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“…In fact, recent study by Mell et al revealed significant difference in cecal microbiotal compositions between the SS and SR rats. 36 Bacteria of the phylum Bacteroidetes were higher in the SS rats compared with the SR rats. Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the SS rats compared with the SR rats.…”

Section: Potential Role Of the Intestinal Microbiome In Regulation Ofmentioning

confidence: 80%

“…Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the SS rats compared with the SR rats. 36 The influence of gut microbiota on the BP regulation is partially explained by the generation of short chain fatty acids (SCFAs), including the beneficial SCFAs (acetate, butyrate, and propionate) and the nonbeneficial lactate by gut bacteria. SCFAs are produced by microbial fermentation of complex polysaccharides (starches and fiber) in the colon.…”

Section: Potential Role Of the Intestinal Microbiome In Regulation Ofmentioning

confidence: 99%

Gut hormones and gut microbiota: implications for kidney function and hypertension

Afsar

Vaziri

Aslan

et al. 2016

Journal of the American Society of Hypertension

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Increased blood pressure (BP) and chronic kidney disease are two leading risk factors for cardiovascular disease. Increased sodium intake is one of the most important risk factors for development of hypertension. Recent data have shown that gut influences kidney function and BP by variety of mechanisms. Various hormones and peptides secreted from gut such as gastrin, glucocorticoids, Glucagon-like peptide-1 impact on kidney function and BP especially influencing sodium absorption from gut. These findings stimulate scientist to find new therapeutic options such as tenapanor for treatment of hypertension by blocking sodium absorption from gut. The gastrointestinal tract is also occupied by a huge community of microbes (microbiome) that under normal condition has a symbiotic relationship with the host. Alterations in the structure and function of the gut microbiota have been shown to play a key role in the pathogenesis and complications of numerous diseases including hypertension. Based on these data, in this review, we provide a summary of the available data on the role of gut and gut microbiota in regulation of BP and kidney function. J Am Soc Hypertens 2016;-(-):1-8.

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Evidence for a link between gut microbiota and hypertension in the Dahl rat

Cited by 313 publications

References 58 publications

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Immune Mechanisms in Arterial Hypertension

Gut hormones and gut microbiota: implications for kidney function and hypertension

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