Physiopathological mechanisms involved in the development of hypertension associated with gut dysbiosis and the effect of nutritional/pharmacological interventions.

The gut microbiota dysbiosis represents a triggering factor for cardiovascular diseases, including hypertension. In addition to the harmful impact caused by hypertension on different target organs, gut dysbiosis is capable of causing direct damage to critical organs such as the brain, heart, blood vessels, and kidneys. In this sense, it should be noted that pharmacological and nutritional interventions may influence gut microbiota composition, either inducing or preventing the development of hypertension. Some of the most important nutritional interventions at this level are represented by pro-, pre-, post- and/or syn-biotics, as well as polysaccharides, polyunsaturated fatty acids ω-3, polyphenols and fiber contained in different foods. Meanwhile, certain natural and synthetic active pharmaceutical ingredients, including antibiotics, antihypertensive and immunosuppressive drugs, vegetable extracts and vitamins, may also have a key role in the modulation of both gut microbiota and cardiovascular health. Additionally, gut microbiota may influence drugs and food-derived bioactive compounds metabolism, positively or negatively affecting their biological behavior facing established hypertension. The understanding of the complex interactions between gut microbiome and drug/food response results of great importance to developing improved pharmacological therapies for hypertension prevention and treatment. The purpose of this review is to critically outline the most relevant and recent findings on cardiovascular, renal and brain physiopathological mechanisms involved in the development of hypertension associated with changes in gut microbiota, besides the nutritional and pharmacological interventions potentially valuable for the prevention and treatment of this prevalent pathology. Finally, harmful food/drug interventions on gut microbiota are also described.

Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge.

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

The Role of the Gut Microbiota in Bile Acid Metabolism.

The gut microbiota has been considered a cornerstone of maintaining the health status of its human host because it not only facilitates harvesting of nutrients and energy from ingested food, but also produces numerous metabolites that can regulate host metabolism. One such class of metabolites, the bile acids, are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. These bioconversions modulate the signaling properties of bile acids through the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate diverse metabolic pathways in the host. In addition, bile acids can regulate gut microbial composition both directly and indirectly by activation of innate immune response genes in the small intestine. Therefore, host metabolism can be affected by both microbial modifications of bile acids, which leads to altered signaling via bile acid receptors, and by alterations in the composition of the microbiota. In this review, we mainly describe the interactions between bile acids and intestinal microbiota and their roles in regulating host metabolism, but we also examine the impact of bile acid composition in the gut on the intestinal microbiome and on host physiology.