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Examining 'synbiotics' and the gut-heart connection

MDlinx Apr 11, 2024

Inflammation is an undeniable key player in the pathogenesis of cardiovascular disease (CVD), involving activation and accumulation of immune cells and releasing inflammatory cytokines.

This inflammation, in part, is regulated by the gut microbiome—and when it also involves the cardiovascular system, it is referred to as the “gut-heart axis.” 


Impacts of a healthy gut


According to a Nutrients review, gut microbiota consist of micro-organisms in the intestinal tract that maintain internal stability.

Wang W, Zhu LJ, Leng YQ, et al. Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases. Nutrients. 2023;15(3):607.



A healthy gut microbiome is anti-inflammatory—consider the following:

  • Mesona chinensis Benth Polysaccharide (MBP) reduces serum, cardiac, and renal inflammation by altering gut microbiota through modulation of the TLR4/MAPK/NF-KB pathway.

  • Probiotics alleviate colitis symptoms and normalize serum cytokine profiles by modulating host immunity and gut microbiota composition—a fall in pro-inflammatory Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), with upregulation of anti-inflammatory Interleukin-13 (IL-13).

  • Paeonol and the Qige Huxin formula (QHF) restore gut microbiota balance, reducing inflammation and offering cardioprotective effects.


Disruption of gut microbiota can trigger inflammatory responses through metabolic alterations, inflammatory factor secretion, and intestinal mucosal damage involved in cardiac failure, atherosclerosis, and chronic kidney diseases.


Health benefits of probiotics


Authors publishing in the International Journal of Molecular Sciences state that probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.“

Hijová, E. Benefits of Biotics for Cardiovascular Diseases. Int. J. Mol. Sci. 2023;24:6292.


Probiotics combat enteric pathogens through antimicrobial bacteriocin production, competitive adhesion to the gut epithelium, mucosal improvement, and immune system modulation. They primarily consist of microbial strains of lactic acid bacteria like Lactobacillus, Lactococcus, Enterococcus, Streptococcus, Bifidobacterium, and yeasts such as Saccharomyces.


Systematic reviews indicate that Lactobacillus and Bifidobacterium strains can potentially mitigate CVD risk factors, including hypertension, type 2 diabetes mellitus (T2DM), obesity, and blood lipid levels. Proposed mechanisms include reduced intestinal cholesterol absorption, assimilation, metabolism, and conversion to coprostanol, bile salt deconjugation, and liver cholesterol and triglyceride synthesis inhibition by short-chain fatty acids. 

Lactobacillus rhamnosus administration may prevent cardiac remodeling after myocardial infarction by improving metabolic dysfunction and attenuating inflammation. At the same time, these strains improve atherogenic indexes and antioxidant markers in diabetic patients. 




The Nature review authors state, "Prebiotics are a group of non-digestible carbohydrates that selectively alter microbial composition and activity.” Criteria for identifying prebiotics include resistance to upper intestinal digestion, fermentation by beneficial gut bacteria, beneficial effects on host health, and stability during the processing of food—which are fulfilled by oligosaccharides like fructans, galactans, human milk oligosaccharides (HMOs) and non-saccharides like polyphenols, according to the International Journal of Molecular Sciences authors.


Prebiotics in high-fiber diets, such as Mediterranean and vegetarian diets, produce anti-inflammatory short-chain fatty acids and act as substrates for Bifidobacterium and Lactobacillus. 

Let's take a closer look at the results from three recent RCTs:




Postbiotics are compounds released or generated through the metabolic processes of the gut bacteria and yeast, per the International Journal of Molecular Sciences report.

SCFAs, notably acetate, are extensively studied postbiotics with potential disease-modifying effects on cardiometabolic diseases. These include gut hormone modulation, reducing inflammation, and enhancing energy expenditure and fat oxidation.


Working together: Synbiotics



Probiotics primarily act in the small and large intestine, while prebiotics mainly affect the large intestine. Combining these substances synergistically enhances the survival of probiotic microorganisms in the gut—thus giving rise to the concept of synbiotics. 

According to International Scientific Association for Probiotics and Prebiotics (ISAPP), synbiotics are defined as “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit.”

Swanson KS, Gibson GR, Hutkins R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. 2020;17:687-701.




Bifidobacterium or Lactobacillus with fructooligosaccharides is one of the most popular synbiotic combinations with clinically proven efficacy.

Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021.


Research demonstrates that synbiotic supplementation leads to the following:

  • Reduction in inflammatory markers, including C-reactive protein, plasma nitric oxide, cholesterol, and malondialdehyde (MDA) in two separate studies

    Pavlidou E, Fasoulas A, Mantzorou M, Giaginis C. Clinical Evidence on the Potential Beneficial Effects of Probiotics and Prebiotics in Cardiovascular Disease. International Journal of Molecular Sciences. 2022; 23(24):15898.


  • Reduced weight and plasma bile acid levels, altered gut microbiota composition, and improved obesity-related markers in obese and overweight patients

  • Lowered BMI, lower fasting blood glucose, improved lipid profile, less insulin resistance, and increased GLP-1 and PYY levels in subjects with metabolic syndrome.

The WHO, FAO, and EFSA heavily regulate dietary biotics to ensure their safety (origin, absence of pathogenic association, and antibiotic resistance profiles) and functionality (survival in the intestinal tract and immunomodulation). Strains must maintain properties during production, storage, and distribution.

What this means for you

As a cardiologist, you can guide your patients to integrate heart-healthy biotics into their diet. Your patients may want to consider adding foods or supplements featuring Lactobacillus and Bifidobacterium strains, along with fiber-rich prebiotic foods such as tomatoes, artichokes, asparagus, and bananas, into their daily routine to support cardiovascular health.


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