An emerging body of evidence suggests that alterations in the composition and function of the gut microbiome could be a driver in the development of cardiovascular disease (CVD); of which atherosclerosis is the most well-established and common cause, forming the pathological basis of several CVDs.
While the research investigating the role of the gut in heart health remains in its infancy, one of the key gut microbiome characteristics identified as playing a role in CVD risk includes a decreased number of butyrate-producer groups (e.g. Faecalibacterium prausnitzii, Butyrivibriocrossotus and Roseburia intestinalis). In fact, previous research has highlighted the importance of short chain fatty acids (SCFAs) in reducing CVD risk.
A reduction in butyrate-producers is linked with localised inflammation and macrophage-derived foam cell formation. This may lead to further gut microbiome perturbations, enhanced gut permeability and translocation of microbes and microbial-derived toxins (e.g. trimethylamine-N-oxide; TMAO and lipopolysaccharide; LPS). In turn, this may activate components of the innate and adaptive immune system, triggering release of pro-inflammatory cytokines, further driving localised and systemic inflammation.
Another potential causative driver of atherosclerosis and a strong predictor of CVD outcomes is increased circulating levels of gut microbiome derived TMAO. Proposed mechanisms by which TMAO may cause harm include promoting oxidative stress and endothelial dysfunction. Indeed, previous studies have shown elevated levels of TMAO in heart transplant patients compared with controls, and in symptomatic heart failure patients.
Circulating levels are influenced by several factors, including diet; in particular, the amount of animal-based products a person consumes. For example, dietary lecithin, choline, and L-carnitine are abundant in red and processed meat, as well as eggs, poultry and fish (in particular, red and processed meats have been associated with a higher CVD risk). This can be metabolized by gut microbes to generate trimethylamine (TMA).
TMA can be converted to TMAO by hepatic enzyme flavin-containing monooxygenase 3 (FMO3) or by gut microbial enzyme TMA monooxygenase. However, identifying the microbial species responsible for TMA formation remains a challenge.
Only recently has the link between the gut microbiome and CVD come to light. The mechanisms underlying this link remains unclear.
Given the gut microbiome is largely shaped by diet, in addition to the role of diet in generating TMAO, the gut microbiome may be considered a therapeutic target in indirectly managing circulating levels of TMAO and subsequent CVD outcomes. Beyond TMAO, other metabolites of interest include Gamma-butyrobetaine (γ-BB) and Trimethyllysine (TML). These have also been shown to be elevated in heart transplant patients.
A plant-based diet appears to be beneficial for gut health and beyond. Compositional differences in the gut microbiome between different dietary approaches (e.g. meat-based, plant-based) are well established.
Practical strategies to optimise the gut-heart axis for patients include:
- Focusing on plants including wholegrains, fruit, veg, nuts, seeds and legumes for fibre, naturally occurring prebiotics and phytochemicals
- Advise healthful lifestyle behaviours including ensuring quality and quantity of sleep and regular physical activity
Amelioration of TMAO through probiotics and its potential role in atherosclerosis (2019)
The Effects of Vegetarian and Vegan Diets on Gut Microbiota (2019)
The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions (2020)
‘The way to a man's heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk (2014)