Gut Microbiota in Hypertension and Atherosclerosis: A Review

Abstract

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.

Gut Dysbiosis and Western Diet in the Pathogenesis of Essential Arterial Hypertension: A Narrative Review

“…An extensive review recently published from Verhaar et al analyzed gut microbiota composition in humans [ 72 ]. The authors reported the association between higher BP values and lower gut microbiota α-diversity in almost all studies [ 30 , 31 , 73 , 74 , 75 , 76 ].…”

“…The authors reported the association between higher BP values and lower gut microbiota α-diversity in almost all studies [ 30 , 31 , 73 , 74 , 75 , 76 ]. It is worth noting that low α-diversity is also present in dyslipidemia, hyperinsulinemia and obesity [ 9 , 72 ]. SCFAs-producing bacteria decrease in hypertensive patients compared to normotensive subjects and these bacteria are obtained by the fermentation of indigestible dietary fibers [ 31 , 74 , 77 , 78 , 79 ].…”

“…SCFAs-producing bacteria decrease in hypertensive patients compared to normotensive subjects and these bacteria are obtained by the fermentation of indigestible dietary fibers [ 31 , 74 , 77 , 78 , 79 ]. Acetate and propionate are absorbed by the gut and enter in the bloodstream, whereas butyrate is only absorbed in small amounts [ 72 ]. Hypertensive patients also showed an increase in microbiota Gram-negative species, with consequent increase of lipopolysaccharides (LPS) [ 72 ].…”

“…Acetate and propionate are absorbed by the gut and enter in the bloodstream, whereas butyrate is only absorbed in small amounts [ 72 ]. Hypertensive patients also showed an increase in microbiota Gram-negative species, with consequent increase of lipopolysaccharides (LPS) [ 72 ].…”

“…Moreover, acetate is able to activate Gpr43 (another G-protein-coupled receptor) in neutrophils present in the lamina propria [ 19 ]. Butyrate was shown to attenuate the pro-inflammatory state consequent to LPS-stimulation [ 72 , 87 ]. In a recent contribution from Robles-Vera et al, the authors demonstrated that chronic oral acetate/butyrate administration prevented the AH onset in spontaneously hypertensive rat (SHR) [ 19 ].…”