Impaired butyrate absorption in the proximal colon, low serum butyrate and diminished central effects of butyrate on blood pressure in spontaneously hypertensive rats

Yang, Tao; Magee, Kacy L; Colon-Perez, Luis M.; Larkin, Riley; Liao, Yan‐Shin; Balazic, Eliza; Cowart, Jonathan R.; Arocha, Rebeca; Redler, Ty; Febo, Marcelo; Vickroy, Thomas W.; Martyniuk, Christopher J.; Reznikov, Leah R.; Zubcevic, Jasenka

doi:10.1111/apha.13256

Cited by 83 publications

(62 citation statements)

References 72 publications

(129 reference statements)

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“…6b). A recent study performed in SHR, showed the same antagonistic results, reporting higher fecal butyrate levels in contrast to circulation levels 40 . They also reported lower expression levels of butyrate-sensing receptors in the hypothalamus of SHR and reduced expression of Slc5a8 transporter in the colon, so they concluded that a reduced availability of serum butyrate in the SHR is possibly due to a diminished absorption in the colon.…”

Section: Scfa In Feces and Plasmamentioning

confidence: 55%

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Calderón-Pérez

Gosalbes

Yuste

et al. 2020

Sci Rep

140

115

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Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.Hypertension is one of the leading risk factors for the development of cardiovascular diseases (CVD) globally, and lifestyle measures are effective as a preventive strategies 1 . In 2015, hypertension based on office blood pressure (BP) reported the highest rates with a global prevalence of 1.13 billion cases, and 150 million in central and eastern Europe regardless of the income countries status 2-4 .The identification of the determinants of hypertension is still challenging although it is well recognized its multifactorial etiology 5 . It has been elucidated the interplay of genetic and environmental factors related with risk-conferring behaviors, such as, smoking, lack of physical activity, alcohol consumption and unhealthy diet 6,7 .Recently, it has been evidenced the role of gut microbiota dysbiosis on the modulation of high BP, both in animal and human hypertension 8 . Mell et al. (2015) were the first to demonstrate the differential fecal microbial composition of Dahl salt-sensitive and Dahl salt-resistant rats 9 . In the same period, Yang et al. (2015) also found a clear gut dysbiosis in spontaneously hypertensive rats (SHR) mediated by a decrease in microbial richness and open Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports www.nature.com/scientificreports/ Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports...

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Section: Scfa In Feces and Plasmamentioning

confidence: 55%

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Calderón-Pérez

Gosalbes

Yuste

et al. 2020

Sci Rep

140

115

View full text Add to dashboard Cite

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“…Intriguingly, fecal SCFA concentrations in humans have been associated with higher blood pressure [ 30 ], while SCFA-producing microbiota are often associated with lower blood pressure [ 31 , 35 , 37 ]. Perhaps, increased SCFA availability in the intestines results in upregulation of absorption mechanisms, which could lead to relatively lower fecal concentrations and higher plasma availability, as was supported by a murine model [ 52 ]. There are no results from human intervention studies with SCFAs to target blood pressure.…”

Section: Gut Microbiota In Hypertensionmentioning

confidence: 99%

Gut Microbiota in Hypertension and Atherosclerosis: A Review

et al. 2020

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Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health. In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis. Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS. Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects. Translocation of LPS into the systemic circulation is a consequence of increased gut permeability. Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways. Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor. In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis. Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets. Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites.

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“…Papers published in Acta Physiologica provide prime examples for the use of BOLD MRI in these research areas. For instance, BOLD measurements in spontaneously hypertensive rats showed that the lack of gut microbiome‐derived butyrate influences the activity of cardio‐regulatory brain regions; this led to the hypothesis that microbial butyrate may play a role in blood pressure regulation 9 . In a rat model of ischemic stroke, dedicated functional MRI techniques were used in a longitudinal study to assess the benefit of early inhibition of the mitogen‐activated protein kinase 1/2 administered at a clinically relevant time point 10 .…”

mentioning

confidence: 99%

“…In a rat model of ischemic stroke, dedicated functional MRI techniques were used in a longitudinal study to assess the benefit of early inhibition of the mitogen‐activated protein kinase 1/2 administered at a clinically relevant time point 10 . As a non‐invasive technique, functional MRI complements various other ‘classical’ methods used to study cardiovascular control, ranging from—mostly invasive—in vivo to ex vivo techniques such as Ca ++ imaging 9,11,12 …”

mentioning

confidence: 99%