Introduction
The connection between gut health and heart disease has become a growing area of interest in medical research. The human gut microbiome, consisting of trillions of microorganisms, plays a crucial role in various bodily functions, including digestion, immunity, and even cardiovascular health. Recent studies suggest that an imbalance in gut bacteria may contribute to the development of heart disease, hypertension, and atherosclerosis. Understanding the intricate relationship between microbiome and cardiovascular health is essential in developing new preventive and therapeutic strategies. This article describes the role of the gut microbiome in heart health, the effects of prebiotics and probiotics, and evidence-based recommendations on the best probiotics for heart health.
Gut health and heart disease
The gut microbiome refers to the diverse population of microorganisms residing in the gastrointestinal tract. These microbes assist in digesting food, synthesizing essential nutrients, and modulating immune responses. Emerging research suggests that gut microbiota influence cardiovascular health through several mechanisms, including inflammation, metabolism, and the production of metabolites like trimethylamine N-oxide (TMAO).
The gut microbiome plays a fundamental role in numerous life-sustaining processes, including the metabolism of dietary nutrients, regulation of immune responses, maintenance of the intestinal epithelium, and synthesis of essential vitamins for instance vitamin K. Due to its extensive influence on various physiological functions, the gut microbiome is increasingly recognized as a ‘multifunctional organ.’
Maintaining a balanced microbial environment in the gut is essential for overall health, as an imbalance—known as gut dysbiosis—can contribute to various CVDs, including hypertension, coronary artery disease, heart failure, and metabolic disorders such as type 1 and type 2 diabetes mellitus (TDM1, TDM2). Atherosclerosis, Coronary Heart Disease, Atrial fibrillation (AF), Hypertension and heart failure and their link with gut microbiome are described below.
The gut microbiome is composed of a diverse ecosystem of microorganisms, including bacteria, fungi, viruses, and protozoa. These microbes interact with the host by modifying gut conditions, such as regulating intestinal pH and producing key metabolites like trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids (BAs). In a healthy state, the gut microbiota remains relatively stable, with Firmicutes and Bacteroidetes being the dominant bacterial organisms. However, alterations in this delicate balance can significantly impact overall health, reinforcing the importance of gut microbiota in disease prevention and management.
The gut microbiome is influenced by a number of factors such as age, sex, diet, obesity, residing place, physical activity, exposure to dust and the influence of antibiotics during infancy. Gut microbiota is also inherited during birth from mother to child and the colonisation of the gut begins in the neonatal phase. According to factors such as an abundance of metabolites and the individual’s immune status, the microbial populations in the gut shift drastically, showing either a dramatic increase or decrease in their populations. The intestinal barrier prevents the translocation of the gut microbiota within the circulatory system, a breach of which has shown an increased incidence of IBDs, diabetes and obesity. However, in terms of CVD incident production of microbial metabolites such as urolithin, protocatechuic acid and indoxyl sulfate is most often associated with CVDs. Various microbial metabolites such as TMAO measured using liquid chromatography-mass spectrometry have shown that their elevated levels in the gut are directly associated with coronary artery disease and heart failure. Research shows that patients with elevated TMAO levels show a 2.5-fold risk of suffering from CVDs. Increased TMAO production is linked to the rapid proliferation of undesirable microbial populations in the gut that synthesize trimethylamine (TMA) lyases. Patients suffering from heart failure also show an abnormal rate of TMAO metabolism and lipopolysaccharide (LPS) biosynthesis.
In addition to this, gut microbiota is closely tied with atherosclerosis, which causes chronic inflammation due to plaque formation in arteries and gradual accumulation of LPS in the endothelium. A dysbiotic gut may contain microbial populations of Helicobacter pylori and Chlamydia pneumoniae. C. pneumoniae is found to induce the pathogenesis of atherosclerosis by targeting macrophages which causes for the appearance of atherosclerotic lesions. The gut microbiome also plays a prominent role in the secondary synthesis of BAs, which is important for eliminating cholesterol. A deficiency of BA can result in elevated cholesterol levels.
(https://www.sciencedirect.com/science/article/pii/S2590097823000216)
TMAO and Cardiovascular Risk
Trimethylamine N-oxide (TMAO) is a metabolite produced when gut bacteria process dietary nutrients such as choline, found in red meat and eggs. Elevated levels of TMAO have been linked to an increased risk of atherosclerosis and cardiovascular disease. A study published in the New England Journal of Medicine found that higher plasma concentrations of TMAO were associated with a significantly increased risk of major adverse cardiovascular events.
(https://www.nejm.org/doi/full/10.1056/NEJMoa1109400)
Additionally, a research article published by Wang et al. in 2011 in a journal called, Nature demonstrated that higher levels of gut bacteria capable of producing TMAO had a greater likelihood of developing heart disease in mice. This highlights the importance of a balanced microbiome in reducing cardiovascular risk.
(https://www.nature.com/articles/nature09922)
Inflammation and Gut Dysbiosis
As already mentioned, an imbalance in gut bacteria, known as dysbiosis, can contribute to systemic inflammation, a key driver of heart disease. Dysbiosis often results in increased intestinal permeability, leading to the leakage of pro-inflammatory bacterial endotoxins into the bloodstream. These endotoxins trigger immune responses, which can accelerate the development of atherosclerosis.
Heart conditions associated with gut dysbiosis
Atherosclerosis
Atherosclerosis and cardiovascular disease have been increasingly linked to microbial infections. Over the past decade, research has revealed that microbial communities residing in different parts of the human body play a significant role in metabolic and cardiovascular disorders. A review article published in 2017 described three key mechanisms by which the gut microbiota may contribute to atherogenesis.
(https://pubmed.ncbi.nlm.nih.gov/27905479/)
To start with, infections—whether localized or systemic—can trigger harmful inflammatory responses, accelerating plaque formation and potentially leading to plaque rupture. In some cases, these inflammatory processes may also contribute to fluctuations in blood pressure. Addressing key challenges in gut microbiome research related to hypertension, such as confounding variables and causation, will be essential for accelerating discovery and clinical translation. Expanding the diversity of study samples worldwide will also enhance our understanding of these mechanisms. Hypertension and it`s link to gut microbiome is described below in more details.
In addition to this, the gut microbiota influences lipid and cholesterol metabolism, which plays a crucial role in the development and progression of atherosclerotic plaques. Dysregulation in microbial processing of lipids can contribute to plaque instability and increase cardiovascular risk.
Finally, dietary components and specific nutrients metabolized by gut bacteria can directly impact atherosclerosis. For example, certain microbial byproducts derived from the digestion of dietary fats and proteins may promote plaque accumulation, whereas others may have protective effects. Understanding these complex interactions will be key to developing microbiome-targeted therapies for cardiovascular disease.
(https://www.sciencedirect.com/science/article/pii/S2590097823000216)
Coronary heart disease
Several clinical studies have indicated that changes in gut microbiota composition may be linked to an increased risk of coronary heart disease. Dysbiosis—an imbalance in gut microbial communities—has been identified as a potential risk factor for coronary heart disease development. In the future, gut microbiota profiling could serve as a valuable diagnostic marker for assessing coronary heart disease risk and progression.
There is a growing consensus that the gut microbiota differs significantly in individuals with coronary heart disease. Research has linked gut microbiota composition to key CHD risk factors, including obesity, diabetes, dyslipidemia, and hypertension. Through its metabolites, the gut microbiota plays a crucial role in fundamental metabolic processes such as cholesterol metabolism, uric acid regulation, oxidative stress, and inflammatory responses—all of which contribute to the development of atherosclerosis and coronary heart dsiease. Current research is exploring interventions such as modifying gut microbiota composition, probiotic supplementation, and faecal microbiota transplantation as potential strategies for preventing and treating CHD. Increasing evidence suggests a causal relationship between gut microbiota and CHD.
(https://pubmed.ncbi.nlm.nih.gov/33063240/)
Hypertension
Over the past decade, a growing body of evidence has established the gut microbiome as a key player in blood pressure regulation. In the last five years, the field has progressed from identifying associations to demonstrating causation, thanks to studies utilizing germ-free animal models, antibiotic treatments, and direct supplementation with microbial metabolites. The gut microbiome influences blood pressure through multiple mechanisms, including microbiome-associated gene pathway alterations triggered by gut dysbiosis.
Microbiota-derived metabolites can have either beneficial effects, such as SCFAs and indole-3-lactic acid, or detrimental effects, such as TMAO. These metabolites regulate blood pressure by activating downstream signalling pathways through specific receptors or by directly modulating immune cell activity. Additionally, gut dysbiosis can compromise the intestinal epithelial barrier, leading to systemic inflammation and disrupting intestinal barrier These disturbances, in turn, influence key regulatory systems involved in blood pressure control, including the renin-angiotensin-aldosterone system, the autonomic nervous system, and the immune system.
Despite these advances, gut microbiome research still faces methodological and technological challenges. Addressing these obstacles requires minimizing confounding factors, establishing clear causal relationships, and improving global sample diversity. The future of microbiome-based blood pressure management may be shaped by emerging clinical trials, precision microbiome medicine, and advanced computational approaches such as Mendelian randomization, all of which have the potential to translate microbiome research into effective therapeutic applications.
(https://pubmed.ncbi.nlm.nih.gov/36631562/)
Atrial fibrillation
Atrial fibrillation (AF), the most prevalent prolonged cardiac arrhythmia, affects over 37 million people worldwide. Numerous clinical and preclinical studies have identified an association between AF and imbalances in the gut microbiome. https://pubmed.ncbi.nlm.nih.gov/36940225/
Obesity significantly increases the risk of AF, and conditions associated with obesity have been directly linked to gut microbiota composition. https://onlinecjc.ca/article/S0828-282X(22)00786-3/abstract)
A recent study published in 2020 Cardiovascular research journal provided strong evidence supporting the role of gut dysbiosis in AF pathogenesis. The researchers demonstrated that age-related gut dysbiosis contributes to AF development by increasing circulating levels of lipopolysaccharides LPS and glucose. (https://pubmed.ncbi.nlm.nih.gov/33757127/)
Another study published in 2020 in Heart and Vessels journal found no significant differences in overall gut microbiota diversity between AF patients and control groups; however, AF patients exhibited lower microbial richness. Compared to healthy controls, individuals with AF had an enrichment of Parabacteroides, Lachnoclostridium, Streptococcus, and Alistipes, while Enterobacter was significantly depleted. The researchers results demonstrated that AF patients had altered gut microbial composition because of dietary habits.
(https://pmc.ncbi.nlm.nih.gov/articles/PMC7788021/)
Furthermore, research by Chinese researchers, which was published in 2020 highlighted distinct gut microbiota alterations across different AF subtypes. Their very interesting findings suggest that both paroxysmal and persistent AF are associated with unique gut microbial shifts. Given that gut microbiota dysbiosis is detectable even in early stages of AF, it may act as an early disease modulator and serve as a potential therapeutic target to slow AF progression.
(https://pmc.ncbi.nlm.nih.gov/articles/PMC7082137/)
Prebiotics vs. Probiotics for Heart Health
Prebiotics and probiotics are two dietary components that influence gut microbiome composition, thereby impacting cardiovascular health.
Prebiotics: Feeding the Beneficial Bacteria
Prebiotics are non-digestible fibers that serve as food for beneficial gut bacteria. They promote the growth of health-supporting microbes such as Bifidobacteria and Lactobacilli, which help reduce inflammation and improve lipid metabolism.
A study published in that consumption of dietary prebiotics has been linked to enhanced feelings of filling and significant reductions in postprandial glucose and insulin levels.
(https://pubmed.ncbi.nlm.nih.gov/24230488/)
Common prebiotics include:
- Inulin (found in onions, garlic, and bananas)
- Fructooligosaccharides (FOS), occur in many fruits and vegetables
- Galactooligosaccharides (GOS), found in dairy products, beans and lentils
Probiotics: Directly Supporting Gut and Heart Health
Probiotics are live beneficial bacteria that, when consumed in adequate amounts, confer health benefits. Several strains of probiotics have demonstrated potential in improving cardiovascular health by reducing cholesterol levels, lowering blood pressure, and mitigating inflammation.
A meta-analysis published in Hypertension journal revealed that probiotic consumption may lead to a modest reduction in blood pressure, with potentially greater benefits observed in individuals with elevated baseline blood pressure. The effect appears to be more pronounced when multiple probiotic species are consumed, the intervention lasts at least eight weeks, or the daily intake exceeds 10¹¹ colony-forming units.
(https://pubmed.ncbi.nlm.nih.gov/25047574/)
Finally, a study published in Clinical Nutrition in 2018 showed that Lactobacillus reuteri supplementation significantly reduced LDL-C by 11.64% (P < 0.001), total cholesterol by 9.14% (P < 0.001), non-HDL cholesterol by 11.30% (P < 0.001), and apoB-100 by 8.41% (P = 0.002) compared to the placebo group. The authors concluded that the deconjugation of intraluminal bile acids reduces the absorption of non-cholesterol sterols, indicating that L. reuteri capsules may serve as a beneficial adjunctive therapy for managing hypercholesterolemia. Deconjugation means disruption of an alternating sequence of double or triple bonds in a chemical compound.
(https://pubmed.ncbi.nlm.nih.gov/22990854/)
Best Probiotics for Heart Health
Certain probiotic strains have shown promise in promoting heart health through cholesterol management, anti-inflammatory effects, and blood pressure regulation. The following probiotics have been studied for their cardiovascular benefits:
- Lactobacillus reuteri – Reduces LDL cholesterol and total cholesterol levels as per the above evidence.
- Lactobacillus plantarum – Improves endothelial function and reduces inflammatory biomarkers in male patient with stable coronary artery disease markers
(https://pubmed.ncbi.nlm.nih.gov/30355158/)
- Bifidobacterium longum – Enhances gut barrier integrity and reduces systemic inflammation.
(https://pmc.ncbi.nlm.nih.gov/articles/PMC10700415/)
- Lactobacillus acidophilus – The consumption of probiotic Lactobacillus, particularly L. reuteri and L. plantarum, has been shown to significantly reduce total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Additionally, the study indicated that synbiotic foods containing L. sporogenes and inulin may provide notable benefits by improving triglyceride (TG) levels and increasing high-density lipoprotein cholesterol (HDL-C).
(https://pmc.ncbi.nlm.nih.gov/articles/PMC5464580/)
A systematic review and meta-analysis was published in Current hypertension reports in 2020 and included a total of 34 studies involving 2,177 adults. Probiotics were found to significantly reduce systolic and diastolic blood pressure, total cholesterol, LDL-C, serum glucose, HbA1c, and BMI while increasing HDL-C levels. However, no significant effects were observed for triglyceride levels.
In summary, probiotics were associated with significant reductions in blood pressure, particularly in individuals with type 2 diabetes and those consuming probiotics for more than 1.5 months. Total cholesterol and LDL-C reductions were most pronounced in participants with diabetes, hypertension, hypercholesterolemia, and those consuming yogurt for less than 1.5 months. Probiotic intake also improved glucose and HbA1c levels, especially in diabetic individuals using lower doses for shorter durations (<1.5 months). Additionally, probiotic supplementation contributed to BMI reduction, particularly in obese individuals taking higher doses for more than 1.5 months.
(https://pubmed.ncbi.nlm.nih.gov/32860083/)
Microbiome and Cardiovascular Health
Advances in microbiome research have paved the way for personalized approaches to cardiovascular disease prevention and management. Techniques such as metagenomic sequencing allow scientists to analyse individual gut microbiota compositions and tailor interventions accordingly.
Recent clinical trials have explored faecal microbiota transplantation (FMT) as a potential therapy for metabolic syndrome and cardiovascular conditions. FMT is an emerging gut microbial-modulation strategy being explored for the treatment of various human diseases, including obesity-associated metabolic disorders.
However, the studies to date reported mixed findings regarding metabolic improvements. Two studies found that donor FMT led to enhanced peripheral insulin sensitivity (measured by the rate of glucose disappearance) at six weeks compared to placebo. Additionally, one study observed lower HbA1c levels in FMT recipients at six weeks. However, no significant differences were found between groups in fasting plasma glucose, hepatic insulin sensitivity, BMI, or cholesterol markers.
While FMT shows promise, its impact on long-term clinical outcomes remains unclear. Further research is needed to better understand how changes in gut microbial ecology and microbiota engraftment influence metabolic health.
(https://pubmed.ncbi.nlm.nih.gov/31557953/)
Furthermore, emerging research is investigating the effects of postbiotics—metabolic byproducts of probiotics—on cardiovascular health. Future studies may establish their role in dietary and therapeutic strategies for heart disease prevention.
Conclusion
The gut microbiome plays a crucial role in cardiovascular health, influencing inflammation, lipid metabolism, and overall heart disease risk. Scientific evidence supports the notion that maintaining a balanced gut microbiota through prebiotics, probiotics, and dietary interventions can promote heart health.
Understanding the impact of gut health on heart disease opens new avenues for personalised medicine and innovative treatments. As research continues to unfold, incorporating microbiome-friendly dietary choices and probiotic supplementation may become a fundamental component of cardiovascular disease prevention strategies.
