Cardiovascular Health and the Microbiome

As science continues to unravel the complexity of the gut microbiome, increasing evidence confirms an association between our microbial communities and heart health. Cardiovascular disease encompasses a range of conditions from hypertension and stroke to myocardial infarction, arteriosclerosis, and atherosclerosis. In this article we explore established and emerging connections between the gut microbiome and our cardiovascular health.

It begins in the mouth…
The mouth is the gateway to the gut, and the oral microbiome is second only to the gut microbiome in terms of size and diversity, hosting over 700 types of bacteria¹.
Research into the link between oral health and heart disease began to increase in the early 1990s after case control studies by Finnish researchers revealed patients with evidence of oral infection were 30% more likely to present with myocardial infarction compared to patients without oral infection².

So, what mechanisms might be involved?

Oral infections and dysbiosis in the oral microbiome, such as increases in lipopolysaccharide (LPS) producing gram-negative bacteria, can trigger local and systemic inflammatory responses, oxidative stress, immune activation, and platelet aggregation associated with cardiovascular disease³, to name a few. Interestingly, research shows that intensive treatment for periodontitis can significantly reduce cardiovascular risk scores, systolic blood pressure, and the inflammatory markers C-reactive protein and IL-6⁴. Maintaining good oral health and a healthy oral microbiome may therefore be an important first step in supporting cardiovascular health.
The gut-cardiac-brain axis
The gut-cardiac-brain axis refers to the dynamic bi-directional relationship between the central nervous system, the gut, and the cardiovascular system⁵. It encompasses all the pathways by which the heart, brain, and digestive system communicate with each other, including:

- Microbial regulation of inflammation.
- Microbial regulation of intestinal permeability.
- Microbial metabolites production; and
- Vagus nerve activity.

Research suggests that relevant changes in the gut microbiome may begin long before the clinical onset of cardiovascular disease⁶. Positioning the gut microbiome as part of a gut-cardiac-brain axis confirms its central role in whole-body health and opens the possibility to explore further the potential for gut-directed interventions for supporting cardiovascular health.

Let's look at the gut-cardiac-brain axis pathways in a little more detail.

Inflammation, immunity, and intestinal permeability
When it comes to cardiovascular disease, it is common to think of inflammation in terms of atherosclerosis, arteriosclerosis, and vascular damage caused by high blood pressure. However, this overlooks other potential underlying inflammatory factors like microbial dysbiosis and a compromised intestinal barrier.

Raised levels of LPS from LPS-producing gut bacteria, and/or a compromised gut barrier increases the tick of LPS translocation into the general circulation. Once circulating, LPS activate the innate immune system, which triggers pro-inflammatory cytokines such as TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8), leading to endothelial dysfunction and increased oxidative stress⁷. Such damage contributes to the development of vascular inflammation and atherosclerosis.

Supporting a healthy gut microbial balance and barrier function, may therefore one way of reducing inflammatory risk factors.

The gut, the heart, and the vagus nerve
One gut-cardiac-brain communication pathway yet to be fully explored is the relationship between gut microbe stimulation of the vagus nerve and heart health for example in the case of cardiac arrhythmias.
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. One small-scale study⁸ exploring the link between gut dysbiosis and AF found that patients with persistent atrial fibrillation of <12 months and persistent atrial fibrillation of >12 months shared common patterns of gut dysbiosis. Overall, the patients with AF had increased numbers of Ruminococcus, Streptococcus, Veillonella, and Enterococcus. Other studies confirm similar findings alongside depleted levels of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila⁹.

It is hypothesised that gut dysbiosis may promote inflammation and affect vagal regulation of the heartbeat via altered metabolite production,⁸ however further research is needed to confirm this.

Microbial metabolites and cardiovascular health
Microbial metabolites act as biochemical signalling molecules, widely influencing many aspects of health. Two microbial metabolites with established roles in heart health are SCFAs and trimethylamine (TMA).
The SCFAs propionate and butyrate are produced by commensal bacteria in the gut from the fermentation of fibre. These metabolites can modulate immune activity and inflammation, with pre-clinical studies suggesting potential beneficial effects for the heart and circulation^10-11.

TMA on the other hand is produced by gut microbes from the breakdown of choline and carnitine (found in animal products). It is transported to the liver where it is converted to the compound trimethylamine-n-oxide (TMAO). Higher levels of plasma TMAO are associated with systemic inflammation and higher long-term mortality risk in patients with cardiovascular disease¹².
Dietary-microbe-metabolite interactions therefore clearly have important implications for cardiovascular health. Plant-rich diets such as the Mediterranean-style diet, which prioritises intake of fibre and polyphenol rich wholegrains, legumes, fruit and vegetables have been shown to reduce cardiometabolic risk factors¹³. In part, this could be due to the abundance of fibre and antioxidant polyphenols in these diets, nurturing commensal microbes and metabolites that support the gut-cardiac axis.

Conclusions
A definitive causal relationship between the gut microbiome and CVD has yet to be established but current research highlights the many direct and indirect links between the microbiome, heart, and circulatory health. These links present an opportunity to utilise nutritional strategies to optimise gut and cardiovascular health.