What Bugs Your Heart?

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

By: Jocelyn Strand, ND

The following arti cle is not endorsed and/or supported by The American Academy of Anti -Aging Medicine. The purposes of this publicati on do not imply endorsement and/or support of any author, company or theme related to this arti cle.

Cardiovascular disease (CVD) now a ects 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 5 th leading cause of death overall.  e good news is that 90% of stroke risk is due to modi able 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 modi able 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.  e 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  e oral and the gastrointestinal microbial communities exhibit the greatest diversity and are innately linked to one another. A  ourishing, heterogeneous microbial community is essential both for oral and systemic health. 8  ese communities are important for human physiology, immune system development, digestion, detoxi cation 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 has 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).  is 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-in ammatory cytokines, chemokines, and adhesion molecules.  ese chemical messengers result in a chronic in ammatory response mediated by both the innate (macrophage activation) and adaptive (T cell activation) immune systems.  e downstream e ect is chronic in ammation, 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 in ammation, damage to mitochondrial DNA in the heart, and increases 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

 e host-microbiome interaction in uences the production of other metabolites including trimethylamine-N-oxidase (TMAO). Increases in Prevotella and decreased Bacteroides resulted in higher levels of TMAO in one study. TMAO is a bacterial metabolite that exerts harmful e ects on the circulatory system, resulting in endothelial dysfunction. It increases chronic in ammation via increased expression of pro-in ammatory cytokines.  ere is mounting evidence that TMAO in uences the progression of CVD, including a direct link to major adverse cardiovascular events. Its e ects 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

In addition to the metabolic e ects of dysbiosis, intestinal permeability allows the translocation of microorganisms from the GI into systemic circulation. Studies have detected the presence of microbial DNA in atherosclerotic plaque and in the fat around the heart. Research shows that these bacteria can be of oral or GI origin. 4 Numerous studies have revealed the presence of bacterial bio lms within fatty deposits of damaged arteries (but rarely in healthy arteries), and have established a signi cant association between infection and coronary heart disease. 3,4 Bio lms are a source of constant and spontaneous inoculation of pathogens and are resistant to immune activity and medications.

ORAL HEALTH AND CARDIOVASCULAR DISEASE

 e 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 10 8 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-in ammatory 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 have a systemic e ect (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 a ects up to 77% of American adults over 30, promotes the release of pro-in ammatory 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

 e teeth provide a non-shedding surface for organisms to establish bio lm in the form of plaque. Neutrophils are the primary immune defense in the mouth but are not e ective against bio lm-associated bacteria. As they attack bio lms, they set o an in ammatory cascade that develops into a gingivitis lesion and increased in ltration 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 bio lm to the gingival bloodstream, pockets may act as reservoirs for pathogens and their metabolites, as well as in ammatory 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 bio lm communities that can sense each other using chemical signaling molecules, a mechanism known as quorum sensing. Bio lms are responsible for 80% of all infections and for most chronic infections.  ey are complex, dynamic structures that react to stimulus in coordinated behavior via intracellular communication. Bio lms 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 e ective option for addressing bio lms and dysbiosis. A study with nearly 400 people found that herbal remedies were as e ective as Rifaximin (the most studied antibiotic related to SIBO) at treating symptoms. An array of herbals and essential oils were used in that trial.  e conclusion reads “Herbal therapies are at least as e ective as rifaximin for resolution of SIBO by LBT (lactulose breath test). Herbals also appear to be as e ective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders. Further prospective studies are needed to validate these  nd ings 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.  e 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, Milk  istle, Echinacea (purpurea & angustifolia), Goldenseal, Shiitake, White Willow, Garlic, Grapeseed extract, Black Walnut (hull and leaf ), Raspberry, Fumitory, Gentian, Tea Tree oil, Galbanum oil, Lavender oil, and Oregano oil. A & L Analytical Laboratories, performed USP E ectiveness Tests, in which this botanical combination was injected with large numbers of disease causing organisms and then cultured for 28 days.  e

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.

“ e advanced botanical combination appears to be e ective at reducing the level of inoculates.” - John Toth, Bio-Services, A & L Laboratories. BOTANICALS ARE EFFECTIVE AGAINST BIOFILMS

Botanicals accomplish control of bio lms 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 bio lms. 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 bio lms highlights their clinical and historical signi cance. 15

Another method of bio lm control is by the inhibition of e ux pumps within cells, called multi-drug resistance pumps. Plants containing tannins, berberine, and certain phenolics have useful e ects as e ux pump inhibitors, demonstrating marked synergy when combined with conventional antibiotics against a variety of both Grampositive 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 bio lm organisms and so help to control the spread of infection. Berberine has been proven bacteriostatic for S. epidermidis. One study showed that sub-minimal inhibitory concentrations blocked the formation of S. epidermidis bio lms. Both Gentian and Goldenseal contain Berberine and are useful additions to the biocidal combination for bio lm control. Grapeseed and Bilberry contain condensed tannins, which prevent adherence of bio lms and may inhibit swarming. 17,18,19,20 One study performed at the University of Binghamton shows the complete eradication of bio lms with exposure to a biocidal formula.

Use of Botanicals in Oral Infections

Botanicals have a long history of use in oral health. A recent study illustrates the potential of a liposomal botanical formula to signi cantly reduce the pathogen load. In this study, 35 pathogens were detected, followed by an 8 week treatment with the biocidal formula. Post testing, pathogenic bacteria was reduced to 4 remaining organisms. The study showed clearance of bacterial, viral, amoeba, and fungal pathogens.

A Novel Approach

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

REFERENCES

1. https://www.acc.org/latest-in-cardiology/ten-points-toremember/2019/02/15/14/39/aha-2019-heart-disease-and-stroke-statistics 2. https://www.heart.org/en/news/2019/01/31/cardiovascular-diseases-affect-nearlyhalf-of-american-adults-statistics-show 3. https://www.ncbi.nlm.nih.gov/pubmed/31469291 4. https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.13250 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746314/pdf/nihms929622.pdf 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057715/ (1) 7. https://www.nature.com/articles/sj.bdj.2016.865 (2) 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274568/ (3) 9. https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_2908-19/_ article – HPV (4) 10. https://www.mdpi.com/2304-6767/6/2/10/htm (5) 11. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0757.1994. tb00019.x?sid=nlm%3Apubmed(6) 12. https://www.ncbi.nlm.nih.gov/pubmed/29563402(7) 13. https://www.nature.com/articles/s41440-019-0260-4.pdf ?draft=collection 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030608/ 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119553/ 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486105/ 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840435/ 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101405/pdf/zac3043.pdf 19. https://www.sciencedirect.com/science/article/abs/pii/S0956713514006586 20. https://www.researchgate.net/profile/Mengfei_Peng/publication/307156613_

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Typhimurium/links/5a295fd1aca2728e05dab087/Bioactive-extracts-from-berrybyproducts-on-the-pathogenicity-of-Salmonella-Typhimurium.pdf

AUTHOR BIOGRAPHY:

While in private practice as a Primary Care Provider, Jocelyn Strand, ND, specialized in GI system disorders, Lyme disease, and autoimmune conditions. In 2019, Dr. Strand became the Director of Clinical Education for Bio-Botanical Research, Inc. drstrand@biocidin.com www.biocidin.com

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