Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder

Abstract

The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes' imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.

Keywords: CVD; FMT; HF; HTN; SCFAs; TMAO.

Figure 1

A diagram depicting the effect of gut bacteria and metabolites on CVD risk factors. SCFAs, short-chain fatty acids; TMAO, trimethylamine N-oxide.

Figure 2

The gut microbiota of the target body’s functioning mechanisms. A low-fiber diet corresponds with decreased short-chain fatty acid butyrate formation, exacerbating dysbiosis and sustaining local and systemic inflammation via bacterial toxin leaks, most notably LPS. A modern Western diet strong in red meat promotes the synthesis of TMA by bacteria, which is then oxidized in the liver to the pro-atherosclerotic metabolite. CVD, cardiovascular disease; TMA, trimethylamine; TMAO, trimethylamine N-oxide.

Figure 3

Gut microbiota composition (A) and diversity and Dysbiosis risk factors (B).

Figure 4

The contribution of the gastrointestinal microbiome to CVD. Choline, phosphatidylcholine, and carnitine are all available in high-cholesterol, high-fat diets. Intestinal microbes convert phosphatidylcholine in the diet to choline, which is then turned into trimethylamine. Hepatic flavin monooxygenases convert TMA to TMAO in the liver. By increasing atherosclerosis and generating agonist-induced platelet activation, TMAO promotes thrombosis. High levels of TMAO in the blood are linked to an increased risk of CVD. Furthermore, a high-fat diet raises the levels of microbe-associated molecular patterns like LPS. Increased intestinal uptake of microbe-associated molecular patterns results in metabolic endotoxemia and low-grade inflammation, both of which worsen atherosclerosis. TLR2 induces arterial thrombosis by increasing the interaction between von Willebrand factor and platelet integrin. Furthermore, intestinal bacteria convert carbs to SCFA and produced by gut microbial fermentation regulate blood pressure, a risk factor for CVD progression. FMO: flavin monooxygenases, SCFAs, short-chain fatty acids; TMAO, trimethylamine N-oxide; TLR2, toll-like receptor-2; LPS, lipopolysaccharide.

Figure 5

Representation of microbial-derived metabolites to CVD. Variations in the composition of the gut microbiome can change the metabolism, allowing bacteria or its fragments and metabolites to enter the circulation more easily. This can aggravate the pro-inflammatory milieu and produce metabolic disturbances, which can lead to CVD. BA, Bile acid; SCFA, short-chain fatty acids; TMA, trimethylamine; TMAO, trimethylamine-N-oxide.

Figure 6

Potential treatments related to improved cardiovascular disease results and improved gut microbiota. The figure illustrates six strategies, i.e., dietary modifications, probiotics, antibiotics, FMT, bioengineering, and herbal treatment.

Figure 7

The correlation between the intestinal microbiome, metabolites, and cardiovascular disease. The intricate connection between dietary components absorbed and other factors influencing the gut microbiota, whose composition then influences their functionality and metabolite production and release, a disruption which leads to dysbiosis, thereby affecting host health and the onset and cause of different cardiovascular disorders. ATP, adenosine triphosphate; BA, bile acid; CO₂, carbon dioxide; CH₄, methane; CVD, cardiovascular disease; H₂S, hydrogen sulfide; PBA, primary bile acid; ROS, reactive oxygen species; SBA, secondary bile acid; SCFA, short-chain fatty acids; TMAO, trimethylamine-N-oxide.