Gut Microbiota and Cardiovascular Disease

Abstract

Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota–dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota–dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)—a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.

Gut microbiome mediates the protective effects of exercise after myocardial infarction

“…44 Microbial transplantation studies could provide strong evidence to support the contribution of gut microbiota in host physiological processes and disease risks. 45,46 Metabolites play important roles in individual physiological stress, disease process and drug development. The application of metabolites in cardiovascular disease is a rapidly expanding field.…”

Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization

“…The gut microbiota significantly contributes to the development of uremic symptoms and long-term consequences of CKD (and to the progression of CKD), but also plays an important role on very early stages of CKD (or even as a factor that initiates kidney injury). For example, several gut-derived uremic toxins have been demonstrated to induce podocyte injury or to stimulate kidney fibrosis [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

“…Nonetheless, the observed changes may be summarized in the following way: The amount of bacteria equipped with urease, uricase and the above mentioned enzymes that participate in tryptophan, phenylalanine, tyrosine, choline, phosphatidylcholine and L-carnitine turnover increase, whereas population of species able to synthesize short-chain fatty acids (such as: Acetate, butyrate, propionate and D-lactate) decreases. The loss of a potential to synthetize short-chain fatty acids (especially butyrate) within the gut lumen exposes CKD patients to the additional health risks [ 39 , 44 , 45 , 46 , 50 , 51 ]. Distinct microbiological profiles of microbiota have been described for CKD in general, but also for particular kidney diseases, such as: Diabetic kidney disease, lupus nephritis and primary glomerular diseases (for example IgA nephropathy) [ 32 ].…”

Berry-Derived Polyphenols in Cardiovascular Pathologies: Mechanisms of Disease and the Role of Diet and Sex

“…The gut microbiota is associated with cardiovascular function and disease (reviewed extensively by Battson et al [ 53 ] and Witkowsky et al [ 54 ]). Physiologic factors, such as age, biological sex, and hormone status, influence characteristics of the microbiota, such as diversity and abundance [ 55 , 56 , 57 , 58 ].…”