March 22, 2021

What Bugs Your Heart?

The Role of Microorganisms in Cardiovascular Health and the Application of Botanicals

Cardiovascular disease (CVD) now affects 48% of adults in the US and is the leading cause of death. Within that category, coronary artery disease resulting in myocardial infarction is most prevalent, while stroke comes in second, and is the 5th leading cause of death overall.

The good news is that 90% of stroke risk is due to modifiable risk factors. As providers, we can work alongside our patients to alter factors that increase risk of CVD. Hypertension (HTN), the most common form of CVD, is a major modifiable risk factor for many other CVDs, including acute coronary syndrome, cardiomyopathy, congestive heart failure, pulmonary hypertension, and stroke.^1,2

Considering the prevalence of CVD and our ability to manage its risk, it is vital that we identify root causes and direct therapeutics accordingly.

One potential target lies in the microbiome. The term microbiome describes the microbial composition of a given area on the body and varies depending on habitat. It is diverse, consisting of bacteria, archaea, fungi, protozoa, viruses, and their trillions of genomes collectively.³

The oral and the gastrointestinal microbial communities exhibit the greatest diversity and are innately linked to one another. A flourishing, heterogeneous microbial community is essential both for oral and systemic health.⁸ These communities are important for human physiology, immune system development, digestion, detoxification reactions, and synthesis of micronutrients. In short, they assist us in maintaining health.

Alterations in the balance (increased pathogen load, reduced commensals, or reduced diversity) of these microorganisms and their functions can result in microbial dysbiosis and have been linked to a host of local and systemic conditions, including cardiovascular disease.^3,4,7

Dysbiosis Creates Inflammation

A healthy gut epithelium provides a barrier for microorganisms and metabolites. When dysbiosis occurs, pathogens release mediators that disrupt the GI mucosa and its ability to function as a barrier to systemic circulation. One of these metabolites is lipopolysaccharide (LPS). LPS is generated in the cell wall of both commensal and pathological gram-negative bacteria. It binds to LPS binding protein, which is then recognized by innate immune cells (macrophages, neutrophils, and dendritic cells). This initiates activation of toll-like receptor 4 (TLR4) and consequently nuclear factor kappa B (NF-kB). NF-kB is a transcription factor that activates a cascade of events including the release of pro-inflammatory cytokines, chemokines, and adhesion molecules. These chemical messengers result in a chronic inflammatory response mediated by both the innate (macrophage activation) and adaptive (T cell activation) immune systems. The downstream effect is chronic inflammation, platelet aggregation, foam cell formation, and ultimately the production of atherosclerotic plaque.^3,4

A two-to-three-fold increase in LPS is called metabolic endotoxemia (ME), which is commonly found in CVD patients. However, even modest increases in LPS have been shown to cause fat deposition, insulin resistance, chronic inflammation, damage to mitochondrial DNA in the heart, and increases in pro-atherogenic endothelial adhesion molecules.⁴

“Microbiota and their metabolites profoundly modulate the progression of atherosclerosis, the most common cause of ACS, stroke, and peripheral vascular disease.”³

The host-microbiome interaction influences the production of other metabolites including trimethylamine-N-oxidase (TMAO). In one study, higher levels of TMAO resulted from increases in Prevotella and decreased Bacteroides. TMAO is a bacterial metabolite that exerts harmful effects on the circulatory system, resulting in endothelial dysfunction. It increases chronic inflammation via increased expression of pro-inflammatory cytokines. There is mounting evidence that TMAO influences the progression of CVD, including a direct link to major adverse cardiovascular events. Its effects are so consistent and remarkable that TMAO is now considered a prognostic tool in patients with cardiomyopathy and possibly a marker for gut barrier permeability.^3,4

Oral Health and Cardiovascular Disease

The role of the microbiota is not limited to the GI tract. In the mouth, there is a complex interplay between microorganisms, the immune system, and “ecological niche” (prevailing properties of the local area) that require balance. We now understand that there are 700+ species of bacteria in the mouth, with a mean of 296. In one milliliter of saliva, there are 108 microorganisms, and as we swallow one liter or more of saliva each day, it is critical to maintain optimal health in the oral microbiome.⁸

Oral health requires balance in the immune-inflammatory state. When there is a dysregulation in the complex interplay between salivary components, immune activity, and existing microbes, dysbiosis occurs causing negative health implications, such as caries, periodontitis, endodontic infection, alveolar bone loss, and tonsillitis.5 Release of mediators from oral pathogens has a systemic effect (e.g. cytokines and prothrombin). People with untreated tooth infections are 2.7 times more likely to have cardiovascular problems—such as coronary artery disease—than patients who have had treatment of dental infections.⁷

Proper oral hygiene has been shown to reduce risk of CVD, including HTN, and stool levels of opportunistic pathogens.¹³ Periodontal disease, which affects up to 77% of American adults over 30, promotes the release of pro-inflammatory cytokines and is well established as a risk factor for AS and other CVD. Furthermore, numerous bacteria associated with pathology in the gut are present in the mouth and can create pathology therein or translocate to the gut and contribute to GI dysbiosis.^7,13 Prevotella, which populates the mouth, is one example of a pathogen that is associated with the production of TMAO, a contributing factor in endothelial dysfunction.⁴

Biofilms Play a Significant Role in the Oral Microbiome and Cardiovascular Health

The teeth provide a non-shedding surface for organisms to establish biofilm in the form of plaque. Neutrophils are the primary immune defense in the mouth but are not effective against biofilm-associated bacteria. As they attack biofilms, they set off an inflammatory cascade that develops into a gingivitis lesion and increased infiltration of T cells and macrophages. Gingivitis progresses into periodontitis, the characteristic periodontal pocket, and the destruction of surrounding tissue. Due to the anatomical proximity of the periodontal biofilm to the gingival bloodstream, pockets may act as reservoirs for pathogens and their metabolites, as well as inflammatory mediators and immunocomplexes that can disseminate systemically.¹¹

“Less than 1 minute after an oral procedure, organisms from the infected site may have reached the heart, lungs, and peripheral blood capillary system”.¹²

Bacteria commonly live in biofilm communities that can sense each other using chemical signaling molecules, a mechanism known as quorum sensing. Biofilms are responsible for 80% of all infections and for most chronic infections. They are complex, dynamic structures that react to stimulus in coordinated behavior via intracellular communication. Biofilms are 10-5,000 times less susceptible to antimicrobials than a single bacterium.⁸

Botanicals Provide a Solution for Infection

Herbal medicines have been utilized by humans in the treatment of infection for thousands of years, and provide a safe and effective option for addressing biofilms and dysbiosis. A study with nearly 400 people found that herbal remedies were as effective as Rifaximin (the most studied antibiotic related to SIBO) at treating symptoms. An array of herbals and essential oils were used in that trial. The conclusion reads “Herbal therapies are at least as effective as Rifaximin for resolution of SIBO by LBT (lactulose breath test). Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for Rifaximin non-responders. Further prospective studies are needed to validate these findings and explore additional alternative therapies in patients with refractory SIBO.”¹⁴

Using the anti-pathogenic properties of more than one botanical in a combination or formula provides a broader spectrum of activity against pathogens. The resulting formulations, or “biocidal combinations,” are powerful allies that may be used to address infection. Testing has illustrated remarkable broad-spectrum antimicrobial activity (in vitro) with a combination containing Bilberry extract, Noni extract, Milk Thistle, Echinacea (Purpurea extract and Angustifolia), Goldenseal, Shiitake extract, White Willow Bark, Garlic, Grapeseed extract, Black Walnut (hull and leaf), Raspberry, Fumitory extract, Gentian, Tea Tree oil, Galbanum oil, Lavender oil, and Oregano oil. A & L Analytical Laboratories, performed USP Effectiveness Tests, in which this botanical combination was injected with large numbers of disease-causing organisms and then cultured for 28 days. The results demonstrated the bacteria and yeast pathogens are completely eliminated in a matter of hours and do not recur over a 28-day period of being cultured.

“The advanced botanical combination appears to be effective at reducing the level of inoculates.” - John Toth, Bio-Services, A & L Laboratories.

Botanicals are Effective Against Biofilms

Botanicals accomplish control of biofilms through several methods. One method is by the inhibition of quorum sensing. Quorum sensing is cell signaling by bacteria and other organisms using autoinducers to determine gene expression, virulence, resistance, and development of biofilms. Botanicals shown to inhibit quorum sensing such as Garlic and Oregano are well known for their antimicrobial ability. This understanding of how they can combat biofilms highlights their clinical and historical significance.¹⁵

Another method of biofilm control is the inhibition of efflux pumps within cells, called multi-drug resistance pumps. Plants containing tannins, berberine, and certain phenolics have useful effects as efflux pump inhibitors, demonstrating marked synergy when combined with conventional antibiotics against a variety of both Gram-positive and Gram-negative organisms. Goldenseal, Black Walnut, White Willow, Raspberry Leaf, and Garlic are a few that have been studied.^15,16

Bacteriostatic agents inhibit the reproduction of biofilm organisms and so help to control the spread of infection. Berberine has been proven bacteriostatic for Staphylococcus epidermidis. One study showed that sub minimal inhibitory concentrations blocked the formation of S. epidermidis biofilms. Both Gentian and Goldenseal contain Berberine and are useful additions to the biocidal combination for biofilm control. Grapeseed and Bilberry contain condensed tannins, which prevent adherence of biofilms and may inhibit swarming.^17,18,19,20 One study performed at the University of Binghamton shows the complete eradication of biofilms with exposure to a biocidal formula.

Use of Botanicals in Oral Infections

Botanicals have a long history of use in oral health with excellent research on their ability to disrupt pathogenic biofilms and function as broad-acting antimicrobials. A recent pilot study by Dr. John Rothchild, DDS, illustrated the potential of a liposomal botanical formula to significantly reduce pathogen load. He used phase-contrast microscopy and examined nine participants that exhibited elevations in pathogenic microorganisms (gram-negative rods and spirochetes) in gingival crevicular fluid derived from the periodontal tissues. Seven out of nine participants had a significant reduction or elimination of pathogens when using liposomal Biocidin LSF for one month. This pilot study helped inform the creation of Dentalcidin LS.

The oral health protocol prescribed by Dr. Rothchild included swishing with 2 pumps of Biocidin LSF for three minutes, and spitting, three times/day. You can learn more about the liposomal oral care solution here. The Dentalcidin™ Toothpaste can be used daily along with the oral care solution for additional support.

A Novel Approach

The wealth of data available on botanicals demonstrates the usefulness of herbals and nutrients as a safe and effective strategy addressing bacterial, viral, and fungal infections. Furthermore, there is ample evidence to suggest that many biofilm-encapsulated infections will also respond to use of these antimicrobial botanicals. Used correctly, the wealth of the planet kingdom is one of our greatest allies in optimizing our health and provides a strong defense against infectious diseases. Botanicals offer a novel approach and deserve consideration where CVD is concerned.

References