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

Abstract

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...

Gut Microbiota in Hypertension and Atherosclerosis: A Review

“…SCFAs, including acetate, propionate, and butyrate, are produced by specific gut microbes by fermentation of otherwise indigestible dietary fibers [ 46 ]. Fecal and plasma levels of SCFA are associated with the abundance of SCFA-producing microbiota in the gut and the intake of dietary fibers [ 36 , 47 , 48 ]. Butyrate-producing microbiota include bacteria from the families Ruminococcaceae and Lachnospiraceae , but also bacteria such as Anaerobutyricum hallii and Anaerostipes spp.…”

Modulation of the Gut Microbiota by Olive Oil Phenolic Compounds: Implications for Lipid Metabolism, Immune System, and Obesity

“…A number of studies have shown that PC consumption induces changes in SCFA levels produced by gut microbiota [99], mainly acetate, propionate, and butyrate. Grapefruit PCs have been demonstrated to raise SCFAs in rats [100], while PCs of red wine and black tea reduced them [101].…”

Gut microbiota metabolites as integral mediators in cardiovascular diseases (Review)

“…These species are positively correlated with systolic and diastolic BP. The same study reported that the level of ScFAs in the plasma was low, whereas the level of fecal SCFAs was significantly higher, indicating that the intestinal ScFA absorption rate is low (58). The ScFA content is positively correlated with Clostridium, Lactobacillus and Blautia XlVa levels, whereas acetic acid, propionic acid and butyric acid levels are inversely proportional to the abundance of Streptococci, Enterococci and other bacteria (22).…”

“…According to the data released in 2015 relating to medical office BP measurements, hypertension has a global prevalence of 1.13 billion and 150 million cases in central and Eastern Europe, respectively. In recent years, studies (58) have found that dysbiosis of the intestinal flora affects BP stability. Metabolites from microbial flora, such as SCFAs and TMAO, are implicated in the pathogenesis of cVd.…”

“…Metabolites from microbial flora, such as SCFAs and TMAO, are implicated in the pathogenesis of cVd. Therefore, it has been suggested that the metabolic products from microflora may be used as targets to treat hypertension (58). ScFAs, which are mainly produced by anaerobic bacteria, such as Lactobacillus and Bifidobacteria, are an important energy source for intestinal microflora and the intestinal epithelial cells of the host, and can inhibit the growth of harmful bacteria, maintain the acid-base balance in the intestinal tract, reduce inflammatory responses, and regulate the host's intestinal immunity.…”