Modulation of gut microbiota by foods and herbs to prevent cardiovascular diseases

Abstract

Dietary nutrients are associated with the development of cardiovascular disease (CVD) both through traditional pathways (inducing hyperlipidemia and chronic inflammation) and through the emergence of a metaorganism-pathogenesis pathway (through the gut microbiota, its metabolites, and host). Several molecules from food play an important role as CVD risk-factor precursors either themselves or through the metabolism of the gut microbiome. Animal-based dietary proteins are the primary source of CVD risk-factor precursors; however, some plants also possess these precursors, though at relatively low levels compared with animal-source food products. Various medications have been developed to treat CVD through the gut-microbiota-circulation axis, and they exhibit potent effects in CVD treatment. Nevertheless, such medicines are still being improved, and there are many research gaps that need to be addressed. Furthermore, some medications have unpleasant or adverse effects. Numerous foods and herbs impart beneficial effects upon health and disease. In the past decade, many studies have focused on treating and preventing CVD by modulating the gut microbiota and their metabolites. This review provides an overview of the available information, summarizes current research related to the gut-microbiota-heart axis, enumerates the foods and herbs that are CVD-risk precursors, and illustrates how metabolites become CVD risk factors through the metabolism of gut microbiota. Moreover, we present perspectives on the application of foods and herbs-including prebiotics, probiotics, synbiotics, postbiotics, and antibiotic-like substances-as CVD prevention agents to modulate gut microbiota by inhibiting gut-derived CVD risk factors.

Taxonomy classification by evise: Cardiovascular disease, gut microbiota, herbal medicine, preventive medicine, dietary therapy, nutrition supplements.

Keywords: Cardiovascular disease; Food; Gut microbiota; Herbs; Microbial metabolite.

Graphical abstract

Fig. 1

Link between gut microbiota and their metabolites and cardiovascular disease (CVD). ① Food and diet can cause CVD risk both through traditional pathways (increasing systemic lipidomics and inflammation) and through the metaorganism pathogenesis pathway (gut microbiota and host). ② Most food is digested and absorbed by the intestine, and nutrients are delivered via the portal vein to the liver for utilization. ③ Undigested food and nutrients can be utilized by gut microbiota for their growth; the byproducts after such utilization are known as gut-microbiota metabolites. ④ The metabolites of the gut microbiota, including trimethylamine (TMA), phenylacetic acid, lipopolysaccharide (LPS), flagellin, peptidoglycan, and short-chain fatty acids (SCFAs), are generated by gut microbiota. Some metabolites are pro-CVD risk factors, but others exert anti-inflammatory effects on human health. Both gut microbiota and their metabolites can translocate to the liver and other organs through the portal vein. ⑤ The liver is the first organ in the body's system to detoxify harmful gut-microbiota metabolites, and hepatic enzymes convert several compounds into CVD risk factors. ⑥ Gut-microbiota–derived metabolites increase CVD risk and systemic inflammation.

Fig. 2

Diet–gut-microbiota–host interaction for cardiovascular disease (CVD) development. Various foods contain pro-CVD precursor biomolecules that are principally derived from animal protein. CVD risk factors and their precursors incorporate trimethylamine (TMA), TMA N-oxide (TMAO), ʟ-carnitine, γ-butyrobetaine (γBB), trimethyllysine (TML), δ-valerobetaine, choline, betaine, sinapine, ergothioneine, and phenylalanine. Lipopolysaccharide (LPS), peptidoglycan, and flagellin also cause systemic inflammation, followed by an increase in CVD risk. The imbalance of the bile acid ratio also causes cardiometabolic disease. The gut microbiome metabolizes non-digestible carbohydrates to short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and thereby exerts anti-inflammatory effects and protects against CVD.

Fig. 3

Application of foods and herbs as prebiotics, probiotics, postbiotics, and antibiotic-like substances for preventing cardiovascular disease (CVD) through the modulation of gut microbiota and their metabolites, as well as the application perspective. These strategies can help understand how to use foods and herbs as preventive medicines and self-health management kits to reduce CVD risk.