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The Gut Connection – Understanding the Role of GI Pathogens and Biofilms in Chronic Disease. Dr. Rachel Fresco, L. Ac., Ph. D Today I want to pull together.

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Presentation on theme: "The Gut Connection – Understanding the Role of GI Pathogens and Biofilms in Chronic Disease. Dr. Rachel Fresco, L. Ac., Ph. D Today I want to pull together."— Presentation transcript:

1 The Gut Connection – Understanding the Role of GI Pathogens and Biofilms in Chronic Disease. Dr. Rachel Fresco, L. Ac., Ph. D Today I want to pull together research on the topic of infections, dysbiosis, biofilms and Endotoxins, and their role in inflammation, and share research on the efficacy of plant based medicine in addressing these in clinical practice. I’m sure most of you have heard of biofilms, but I will take a moment for a quick review here as we begin. ©2014 Rachel Fresco. Reproduce with permission only. All Rights Reserved

2 Anatomy of a Biofilm Communities of microbial cells surrounded by a secreted polymer, called the extracellular polymeric substance or EPS which is an endotoxin. Discovered by Anton Von Leeuwenhook the “father of microbiology” when he inspected dental plaque Composed of multiple organisms, including both aerobic and anaerobic bacteria and/or fungal species More than 80% of all microbial infections have developed biofilms beginning in as little as two weeks from the onset of infection Cause 2 million HAI infections and 100,000 deaths annually Biofilm bacteria can resist up to 5000 times the antibiotic concentration that would normally be needed to resolve infections. Biofilms are multi organism communities protected in a polymer coating called the Extracellular Polymeric Substance. A variety of aerobic and anerobic bacteria, yeast and fungal species can be found in biofilms. In the beginning of biofilm development there is the initial attachment of free swimming micro-organisms to a surface, which is reversible. Then a more permanent chemical attachment is made comprised of single layer of organisms. Once sufficient numbers are present, they then start to produce the EPS matrix. As growth continues a vertical development can be seen, finally, multiple towers with channels in between like small cities are found, and so a complete biofilm is formed. Within these communities metabolic activities are integrated, and developmental sequences, not unlike those of multicellular organisms, can be detected. This Mature biofilm then begins seeding and dispersal of more free swimming organisms and the cycle continues at another site. Intervention in the attachment and development phase, and breaking up the EPS will be important considerations in treatment. Given that 80% of all infections have a biofilm component, and that the colonies begin to form in as little as two weeks, is is any wonder that these infections are so challenging? According to the NIH, 2 million HAI infections and 100,000 deaths are attributed to biofilms every year. In 2011 a specific protein in S. epidermidis biofilm known as Phenol Soluable Modulin Beta was discovered. This explains why phenolic botanicals have been so useful in addressing chronic infections, and we will look more closely at why later in this presentation. Biofilm encapsulated infections are difficult to treat with conventional drug therapies, resisting up to 5000 times the concentration of antibiotics usually needed. Recurrence, and spreading of infection is common as part of a biofilm life cycle. Drug resistant infections like MRSA and C. Difficile are rampant. In the local hospital, a nurse friend shared with me that MRSA was found on lamps, chairs and other surfaces in patient rooms even after the rooms were cleaned and made ready for the next patient.

3 Structure of Lipopolysacchride (LPS) Endotoxin
What is LPS – Component of Biofilms? LPS is an endotoxin from gram negative bacteria and is a component of Biofilms. LPS can be a factor in all autoimmune diseases, alzheimers, chronic fatigue, fibromyalgia, and a broad range of chronic disorders. Here is an image of what E. coli LPS looks like. Where does it come from? LPS passes from the GI tract including the oral cavity to virtually anywhere in the body, setting up a cytokine response, inflammation and autoimmunity. Structure of Lipopolysacchride (LPS) Endotoxin

4 Biofilm Associated Infections
Chronic Sinusitis Biofilms of both yeast and/or bacteria are found in 80% of patients undergoing sinus surgery. Pulmonary Infections Bacterial and fungal biofilms can cause chronic infection such as pneumonia, cystic fibrosis, and tuberculosis. Kidney Stones Stones consist of a complex composed of bacterial biofilm, and mineralized stone material. Heart Disease Inflammation of the smooth membranes which line the inside of the heart is caused by a complex biofilm composed of both bacterial LPS and host components. Biofilms have been found on stents and other cardiac prosthetics. Staph aureus biofilm on a catheter What are the more common biofilm related infections? Intubation in hospitals is another common way biofilms are introduced into the lungs causing life threatening pneumonia. Sometimes bacteria such as staph areus introduced in dialysis of kidney patients also causes pneumonia, as seen in one study. MRSA Pseudomonas A. biofilm inside the alveoli in the lung

5 Biofilm Associated Infections
Inner Ear Infections The majority of ear infections, (OM) are caused by biofilm bacteria and or fungal infection. OM is the most common illness for which children visit a physician, receive antibiotics, or undergo surgery in the United States. Two thirds of post operative tissue cultures have biofilms. Periodontal Disease Over 500+ microbial biofilm species colonize the human mouth, causing tooth decay and chronic gum disease, and these bacteria can migrate throughout the body causing a variety of infections. In many cases of periodontal infection C. albicans and S. aureus co-colonization makes it difficult to treat. Chronic Wounds Biofilms have been implicated in chronic wounds, including antibiotic resistant Staph such as MRSA. Otitis Media Biofilm Haemophilus influenzae is also one of the pathogens found in chronic Ear infections. With 2/3 cases containing biofilms, it is easy to see why ear infections are the #1 cause of children’s visits to a physician. Unless treatment is directed at both fungal and bacterial components, as well as the biofilm, the infection can recur. Biofilms comprised of Candida and Staph together are a major cause of periodontal disease. MSRA is seen in chronic skin infections, and is more and more commonplace outside of the hospital. I will be discussing the 5 ways to successfully treat biofilms with plant based medicine later on. Dental Biofilm MRSA

6 Autism, MS, Lyme Chronic Neuro-Excitotoxicity Brain and nerve cell loss, as seen in Autism, MS, and Parkinson’s % of MS patients test positive for infection % of autistic children have abnormal yeast and bacterial loads. Biofilm Infections Found Include: Yeast Bacteria Viruses Parasites Lyme Disease and co-infections Mycoplasma Chronic infections need to be treated to stop persistent activation of microglia and nervous system damage. Resting Microglia Infections cause chronic neuro-excito toxicity, and can be caused by any type of pathogen % of MS patients and more than 80% of children with autism test positive for some type of infection. I borrowed the pictures of the nerve cells from a presentation by Dr. Anju Usman, who specilizes in Autism and Biofilm treatment. Microglia make up the innate immune system of the central nervous system and are key cellular mediators of neuroinflammatory processes. Dr. Eva Sapi shows that Biofilms of borrelia contain Spirochete, cyst, and granular stages . Activated Microglia

7 LPS causes activated Microglia
Neuro-inflammation plays a prominent role in the progression of Alzheimer's disease Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors Here infusion of LPS creates brain inflammation leading to a decline in hippocampal NMDA-R1 receptors which plays a prominent role in Alzheimers. What is LPS? What is the relationship of LPS and Biofilms? Where is this LPS coming from? Affiliation: Arizona Research Laboratories, Division of Neural Systems, Memory & Aging; University of Arizona, Tucson, AZ, USA. Rosi S, Ramirez-Amaya V, Hauss-Wegrzyniak B, Wenk GL - J Neuroinflammation (2004) LPS causes activated Microglia Figure 1: Confocal microscope images of activated microglial cells MHC II (green OX-6 positive) in the Dentate Gyrus. Rats infused with aCSF (A) had only a few activated microglia scattered throughout the brain. Chronic infusion of LPS into the 4th ventricle produced high activated microglia distributed throughout the hippocampus (B). Higher magnifications of an activated microglia (C, D Rosi S, Ramirez-Amaya V, Hauss-Wegrzyniak B, Wenk GL - J Neuroinflammation (2004)

8 One just has to type LPS into the pub med search engine to find studies like this one on Rheumatoid Arthritis. In the British Journal of Pharmacology, this study showed that….the systemic….. Anti Collagen antibodies and enchanced secretions of cytokines, Thus LPS may play a role in the exacerbation of auto-immune diseases. In summary, the systemic injection of LPS resulted in the reactivation of Collagen-induced arthritis in mice that was associated with the increased production of anti-CII IgG and IgG2a antibodies as well as the enhanced secretion of cytokines including IL-12, IFN-γ, IL-1β, and TNF-α. Thus, LPS may play a role in the exacerbation of autoimmune diseases.

9 Here’s a study that just came out last month on LPS and Rheumatoid Arthritis.
But what about Gram Postive bacteria. What kind of endotoxins do they have? What about lipoteichoic acid (LTA; Gram-positive bacteria)? These results suggest that molecular associations between LPS/TLR4/collagen type II in chondrocytes up-regulate the NF-kappaB and PI-3K signalling pathways and activate pro-inflammatory activity.

10 Lipoteichoic acid or LTA is similar to LPS and is the endotoxin of gram positive bacteria. I have not heard mention at any conference yet about LTA, but it only makes sense that if gram negative batceira produce endotoxins, so do gram positives. Now, we know that within as little as two weeks of any infection biofilms begin to form, so it makes sense that in any chronic disease, we have infiltration of these toxins. So where does this often occur? It can occur anywhere along the GI tract. Thus, LTA shares with LPS endotoxin many of its pathogenic properties. In animal studies, LTA has induced arthritis, nephritis, uveitis, encephalomyelitis, meningeal inflammation, and periodontal lesions, and also triggered cascades resulting in septic shock and multi-organ failure.

11 Biofilms, LPS, LTA in G.I. Disease Intestinal Dysbiosis and Leaky Gut Syndrome
Perforation of the GI lining by pathogenic bacteria, yeast or parasites, resulting in LPS and LTA endotoxin translocation. Our intestines have a surface area the size of a tennis court, so the potential for pathogenesis as huge. That’s why Is gut the root of health and disease? Leaky gut is one of the main causes of compromised immunity as pathogens and toxins are disseminated throughout the body. As we are learning, a wide range of conditions from auto immune disorders to arthritis are seen, as well as food allergies, and a host of other complaints all caused by pathogenic bacteria, yeast and endotoxins that have translocated into general circulation. One study that was published in Annals of the Rheumatic Diseases in 2004 found a 100% correspondence of fibromyalgia with Small Intestine Bowel Overgrowth. This is why one of the first things that needs to be addressed with any new patient is the integrity of the GI tract.

12 Chronic GI Dysbiosis: Linked to arthritis, cardiac disease, fibromyalgia, auto-immune disorders, nerve and brain cell inflammation. Candida Hyphal forms invade epithelial cells and cause tissue damage. Toxic by-products of yeast such as acetaldehyde are carried to distant parts of the body including the brain. AH damage to red blood cells impairs oxygen transport. (20% of oxygen intake is used by the brain). C. Difficile Infection 3 million cases in hospitals in the US, one study found 20% of nurses uniforms contaminated by the end of a workday. Not killed by alcohol, soap and water or bleach is needed. Chronic Inflammation Seen in acid reflux, GERD, colitis, Crohn’s disease. Neurotransmitter Disregulation Sleep and mood disturbances. You can only imagine the problems with absorption of nutrients, and systemic toxicity caused by infections such as Candida and C Difficle. If you want heart first hand about the devastating effects of candida, please speak with Karen Hubert, who is one of our clinical consultants. Karen was in a wheelchair and diagnosed with MS and Alzherimers, and showed signs similar to those seen in Autism before finding and successfully treating the Candida infection that caused her severe illness. C. Difficile Biofilm

13 Bacterial lipopolysaccharides (LPS) variably modulate in vitro biofilm formation of Candida species.
According to this study, the gram negative bacteria and candida have brokered a deal so to speak to help each other thrive in human hosts. This is why a broad spectrum approach is often needed that addresses yeast and bacteria as well as the biofilm that is harboring them.

14 Zonulin and Systemic Inflammation: Celiac / Gluten Intolerence and Leaky Gut Syndrome
When the finely-tuned Zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extra-intestinal autoimmune, inflammatory, and neoplastic disorders can occur. Next I want to show a couple of slides borrowed from Dr. Alessio Fasano, not just because he is so cute, but after hearing him speak here last year, I have come to have a much better respect for the role of Zonulin in intestinal permeability, and it’s relationship to LPS I am sure many of you are familiar with Dr. Fassano’s work with Celiac disease. Zonulin, is a protein produced by the body in response to exposure glycoproteins in grains or intestinal pathogens. It is the only physiological modulator of intercellular tight junctions that is involved in transport of macromolecules and, therefore, in tolerance/immune response imbalances. Dr. Fasano concluded that the loss of intestinal barrier function is the major contributor to autoimmune pathogenesis. Dr. Alessio Fasano Director Center for Celiac Research Mass General Hospital for Children Mechanisms of gliadin-induced zonulin release, increased intestinal permeability, and onset of autoimmunity. From Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

15 LPS, Zonulin and Systemic Inflammation: Intestinal Dysbiosis and Leaky Gut Syndrome
Lipopolysaccharides (LPS) are endotoxins comprised of structural components of Gram-negative bacteria that may be discovered in plasma through an Intestinal Antigenic Permeability Screen. The presence of LPS in the blood is a ”smoking gun” for intestinal permeability caused by intestinal dysbiosis, and may indicate a chronic biofilm encapsulated infection Dr Brady and Dr. LaValle’s presentations will be going over the topic of autoimmunity and gut related disorders this weekend, so I am just going to touch on them quickly here. There are serum tests for Zonulin and LPS available from Cyrex labs. I do not have a financial relationship tot cyrex, but am a big fan of Dr. Aristo Vodjani who created this test. Intestinal Antigenic Permeability Screen Actomyosin IgA Occludin/Zonulin IgG Occludin/Zonulin IgA Occludin/Zonulin IgM Lipopolysaccharides (LPS) IgG Lipopolysaccharides (LPS) IgA Lipopolysaccharides (LPS) IgM

16 Elevated serum zonulin was detected in 70% of autoimmune subjects
Ann. N.Y. Acad. Sci. 1165: 195–205 (2009) Elevated serum zonulin was detected in 70% of autoimmune subjects Dr. Vodjani states: When the zonulin/occludin pathway is deregulated in genetically susceptible individuals, intestinal and extraintestinal inflammatory and autoimmune disorders can occur. In these cases, the intestinal tight junctions allow the passage of macromolecules from the intestine to the submucosa, and the regional lymph nodes stimulate the immune system to mount cellular and humoral immune responses against various tissues or organs. This theory is echoed and strengthened by different studies, lending support to the understanding of the role that the gut-associated lymphoid tissue (GALT) plays in the excessive increase in intestinal permeability during development of autoimmune diseases, such as celiac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis. This finding was verified by measuring the zonulin levels in the sera of patients with autoimmune diseases. Elevated serum zonulin was detected in 70% of the subjects

17 Physiol Rev 91: 151–175, 2011 Among the several potential intestinal luminal stimuli that can trigger zonulin release, we identified small intestinal exposure to bacteria and gluten as the two more powerful triggers.

18 Autoimmune Disease “Emerging evidence has suggested the involvement of environmental factors such as infections and xenobiotics, and some dietary proteins and their antibodies in the pathogenesis of many autoimmune diseases. These antibodies appear in the blood years before presentation of symptoms in various disorders. Therefore, these antibodies may be used as biomarkers for early detection of various diseases.” ALTERNATIVE THERAPIES, jan/feb 2013, VOL. 19, NO.1 Dr. Aristo Voljdani, Ph. D. In an article this year in Alternative Therapies Dr. Artsto Voljdani states: Dr. Voljdani, has contributed greatly to lab assessment with tools such as the Cyrex arrays and Immunosciences Labs Autoimmune Profiles.

19 dissemination of LPS and systemic immune activation
Mucosal Immunol July ; 3(4): 387–398. Translocation of microbial products and the resulting immune activation have not only local consequences within the GI tract, but are also associated with systemic dissemination of LPS and systemic immune activation And again, this information is not limited to those of us in Functional and Integrative medicine. Here an article in Mucosal immunity from 2010 states….

20 SIBO -Small Intestine Bacterial Overgrowth
Of the 42 fibromyalgia patients, 100% were positive for SIBO. overgrowth LPS From Viral Infected E. Coli Theophil Hey, MD and colleagues found that 80% or more of those with fibromyalgia are harboring a virus. It isn’t a human virus, but it is a virus that infects the E coli bacteria that is living in their intestines. His testing showed that only 12% of the people without fibromyalgia had this infection. When a group of fibromyalgia patients were tested during a flair of symptoms, 62 out of 63, or 98% tested positive for this problem. When the infected E coli die, they burst and produce fragments of the E coli shell. Gram-negative bacteria, like E. coli, have a layer in their shell of a fatty substance called lipopolysaccharide (LPS). LPS is highly toxic to humans.

21 J Affect Disord. 2007 Apr;99(1-3):237-40. Epub 2006 Sep 27.
Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. Maes M1, Mihaylova I, Leunis JC We measured the above immune variables as well as the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale in 41 patients with CFS before and months after intake of NAIOSs. RESULTS: Subchronic intake of those NAIOSs significantly attenuates the initially increased IgA and IgM responses to LPS of gram negative bacteria. Up to 24 patients showed a significant clinical improvement or remission months after intake of NAIOSs. The present study examines the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in CFS patients both before and after intake of natural anti-inflammatory and anti-oxidative substances (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet during months. The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in CFS. The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS.

22 LPS, Zonulin and Systemic Inflammation: Intestinal Dysbiosis and Leaky Gut Syndrome
Clinical Goals: Eliminate GI Dysbiosis due to pathogenic bacteria, yeast, fungus and parasites. Address biofilms and systemic infections, reduce LPS, LTA translocation Eliminate allergens from the diet. Support detoxification: liver and toxic metals, LPS burden Raise antioxidants such as glutathione. Support beneficial organisms with pre and probiotics. Heal gut lining with Vit D-3, glutamine, other support supplements These are really fundamental protocols in any patient with chronic inflammation or any long term illness. As we have seen, Chronic inflammation is seen in myriad conditions including Diabetes, Heart Disease, Chronic Fatigue, Lyme disease, Neurological conditions, Depression, and virtually all Autoimmune Disorders,. These are caused or exaggerated by altered intestinal ecology due to diet and/or the presence of pathogens that alter intestinal permeability and create translocation of endotoxins such as LPS and LTA.

23 Antibiotic Therapy Can be life-saving, however…
Overuse has lead to resistant strains and pollution of the environment. Are often ineffective in Biofilm and “superbug”related infections May disturb normal GI flora, causing overgrowth of yeast or bacteria, as seen in C. Difficile infection Research suggests botanicals may assist antibiotic effectiveness So how do we deal with GI pathgens? We can use drug therapes, but….. But there is good news! Botanicals may be able to work in some cases where the drug therapies have failed. There is a great deal of research available on treatment of chronic infections using plant based medicine. Antibiotics known to cause C. Difficile: Clindamycin Ampicillin Amoxicillin Cephalosporins Occasionally cause C. Difficile: Penicillin Erythromycin Ciprofloxacin

24 Biofilm Control: Utilizing Plant Based Medicines
Inhibition of Quorum Sensing Inhibition of Initial Attachment Phase of Biofilm Colonies Inhibition of Swarming Motility Multi-Drug Resistance Pump Inhibitors Bacteriostatics / Bactericidals In this research I have discovered 5 distinct ways that botanicals can be used to effectively treat biofilm infections. Ideally, treatment will include botanicals with activity in each of these areas: This University of Binghamton study shows effect of botanical on Pseudomonas and Candida Biofilms. 24 hour Exposure to Botanical Combination

25 Inhibition of Quorum Sensing
Cell signaling by organisms using auto inducers called Quorum Sensing determines gene expression, virulence, resistance, and the development of biofilms. Botanicals which are known to inhibit Quorum Sensing: - Garlic - Oregano - Bilberry - Bladderwrack Quorum Sensing is like a Facebook friend request amongst bacteria or other pathogens. Once sufficient numbers are gathered then the biofilm can begin to form. Stopping this communication, like losing internet access, prevents this activity. It is no surprise that Garlic and Oregano are on this list since they have been used for millenia to fight infection.

26 Essential Oils: Prevention Adhesion and Disrupting or Destroying Biofilm Components Remember at the beginning I mentioned Phenol Soluable Modulin Beta in Biofilms, that’s where the essential oils and phenolics come into play. Phenolics such as Thymol interact with surface proteins of bacteria, leading to an alteration of the cell surface and interrupt the initial attachment phase of biofilm formation Essential Oils may prove to be most useful in treating multi drug resistant gram negative bacteria such as Pseudomonas, Escherichia and Acinetobacter.

27 Condensed Tannins: Powerful OPC’s Control Biofilm Development by
Inhibition of Swarming Motility of Pathogenic Organisms Grape Seed and Bilberry contain condensed tannins that prevent adherence of biofilms, and may inhibit swarming motility of bacteria. OPC’s are also potentiators for Vit C, providing numerous benefits in cellular health and anti-aging medicine. In this picture we see the benefits of OPS called Condensed Tannins in controlling spread of biofilms infections. Representative images of P. aeruginosa swarming motility under control conditions (A) and in the presence of Cranberry (B) and Pomeranate (C) (both 100 μ/ml).

28 Efflux Pump Inhibitors:
Inhibition of Multi Drug Resistance Pumps Tannins, berberine, and certain phenolics have useful effects as efflux pump inhibitors. Research indicates that these botanicals can potentiate conventional antibiotics and increase their effectiveness against a variety of both gram positive and gram negative organisms. Goldenseal, Black Walnut, White Willow, Raspberry Leaf Bladderwrack, Uva Ursi, and Garlic are a few botanicals that have been studied as Efflux Pump Inhibitors. This ability to inhibit multi drug resistance pumps is of particular interest to practitioners treating Lyme Disease or other infections with antibiotic drug therapies.

29 Formulation Rationale for Botanical Combinations:
Only medical grade botanicals contain enough of the active ingredients to be clinically effective. Like a symphony, individual components must be in harmony. The goal in formulation is achieved when a maximum result is produced without stressing the body or causing unwanted side effects. What is the best way to take advantage of all the benefits of the plant medicines in treating biofilms? Most useful is a synergetic combination of medical grade extracts, that will give the best clinical results without causing any toxicity or side effects. For example, although we know Oregano Oil is a valuable ingredient, often if taken alone it can cause stomach upset and therefore poor patient compliance.

30 Combination Botanical Formulas
Broad Spectrum of activity against gram positive and gram negative bacteria, yeast, fungus, parasites and viruses. Inhibition of biofilms through more than one mechanism of action. Acts both systemically and in the digestive system, and may be used in acute or chronic infection. Contains immune system modulators to up-regulate the body’s own defenses. Supports clearance of toxins through activation of drainage pathways of the liver and kidneys. Reduces inflammation and promotes healing of tissues to reverse damage due to leaky gut. A synergistic blend to produce desired results without side effects or stress on organ systems.

31 Botanical Combination Formulas Address:
Dysbiosis and Leaky Gut Candida Lyme and co-infections Skin infections Viral conditions Upper respiratory infection Dental/Gum infection Urinary tract infection Prostate inflammation Auto-immune disease Elderly or at risk individuals During heavy metal chelation Adjunct to cancer treatments Any acute or chronic infection In researching the individual ingredients of Biocidin, we find that they show: Biocidin is really useful when dealing with dysbiosis as typically there is more than one type of pathogen and biofillms present. Even in difficult to treat cases of C. Difficle that have failed Vancomycin we have seen clearance in before and after lab tests. In organic acid testing for arabinose, and indicator of Candida, one autistic child had a pretreatment level of 700, that reduced to 11 after 6 weeks on Biocidin. His tantrums and intense behaviors were greatly reduced, and the parents were very grateful to their doctor. In lyme there are co-infections as well, that include piroplasms and other parasites. Babesia can cause intense intestinal pain, and constipation. Typically with cold and flu there may be both viral and bacterial infection, and we have seen good effects in all herpes family viruses as well as upper respiratory infections. I love the story told to me a few years back by one of our physician customers in California, about his daughter that played Water Polo on a national team and came down with Mono. She had always told her dad that he was a quack for using alternative therapies, and she would only take the antiviral drugs for her condition. Weeks went by and she had no improvement, and still could not swim, so reluctantly she agreed with his suggestion to take Biocidin and Olivirex. After two weeks on these two formulas she was back in the water and had to admit her dad was not a quack after all!

32 USP Effectiveness Testing of Botanical Combination
Demonstrates inhibitory activity of against both gram positive and gram negative bacteria, yeast and fungus. Bilberry extract, Grape Seed extract, Milk Thistle, Echinacea, Goldenseal, Shiitake, White Willow, Garlic, Black Walnut (hull and leaf), Raspberry, Fumitory, Gentian, Noni, Tea Tree oil, Galbanum oil, Lavender oil, Oregano oil Copies of this USP effective test are included in our professional literature. Here the activity against yeast, fungus, gram postivie and gram negative bacteria in planktonic form were tested and as you can see the results are really impressive. The lab director actually called me up when he saw the result on Aspergillis Niger, black mold, as is very hard to kill. Text Text

33 Bacteriostatic and Bactericidal Botanicals
Bacterostatics: Prevent Replication of Bacteria. Berberine containing plants such as Goldenseal and Gentian have demonstrated powerful bacteriostatic action. One study showed the effectiveness of berberine against Staph. epidermidis, one of the most common causes of skin infections. Sub-minimal inhibitory concentrations block the formation of S. epidermidis biofilm. Bactericidals: Terminate Bacteria Olive Leaf , Goldenseal, Bilberry, Grape Seed, Shiitake, Noni, Black Walnut, Garlic, Gentian and Fumitory are potent bactericides. Oregano, Tea Tree , Lavender and Galbanum oils are essential oils with excellent antimicrobial activity. This ability of Berberine to inhibit multi drug resistence pumps in addition to being bacteriostatic and bactericidal makes it an excellent addition to any formula addressing infection.

34 Combining Antimicrobial Ingredients Provides Maximum Effectiveness
Goldenseal Contains Berberine with broad antimicrobial activity. Berberine has also been shown to kill a wide range of organisms, such as those that cause candida (yeast) infections, viruses, and various parasites such as tapeworms and Giardia. Berberine may also activate white blood cells, making them more effective at fighting infection and strengthening the immune system, in addition to helping to remove biofilms. Gentian Used to purify the blood since discovered around 167 B.C., Gentian is a digestive bitter. It also increases the activity of the liver and gall bladder to improve their function, and is used to improve absorption of nutrients, especially iron. Like Goldenseal it also contains Berberine with a broad spectrum of activity. Echinacea Angustifolia and Purpurea Contains active substances that enhance the activity of the immune system, relieve pain, reduce inflammation, and have antiviral, and antioxidant effects. We have seen how combining botanicals provides maximum effectiveness. Goldenseal and gentian are two of my favorite berberine containing plants, and have a broad range of effects of both biofilm encapsulated infections, parasites and other pathogens.

35 Combining Antimicrobial Ingredients Provides Maximum Effectiveness
Olive Leaf In vitro studies have shown that Oleuropein can inhibit the growth of viruses, bacteria, fungi and parasites via complex and novel methods including the inhibition of enzymes necessary for bacterial growth and weakening the cell wall of pathogens. Garlic A potent antioxidant and antimicrobial, garlic has been used as medicine for thousands of years. Recent research points to it’s cardiovascular benefits, anti- cancer properties and immune enhancing properties, including inhibition of MDR pumps and Quorum Sensing. Black Walnut Containing valuable tannins Black Walnut is not only anti-parasitic but also anti-fungal, anti-viral and antimicrobial. Extract of black walnut is reported to treat eczema, herpes, psoriasis, fungal infections, and both skin and internal parasites. Olive leaf and the active ingredient Oleuropein is one of the best documented antimicrobials. If you have ever been to Greece you will be amazed at the health of the ancient olive groves there. Nature has provided these trees with the ultimate weapons against pests, and by using the extract of olive leaves we share in the benefits. There are so many studies on antimicrobial properties of Garlic and Allicin, it would take more time than we have to go over them, but of special interest in the treatment of biofilms is the inhibition of Multi Drug Resistance Pumps and Quorum Sensing. Black Walnut is an excellent source of plant tannins, and is also broad-spectrum against a wide range of pathogens.

36 Medical Grade Essential Oils
Oregano Oil of Oregano contains two key compounds, carvacrol and thymol. Studies have shown that both of these compounds have significant effects on harmful microorganisms and biofilm infections. In addition, thymol can reduce bacterial resistance to common drugs such as penicillin. Thymol has been shown to be an effective fungicide, particularly against fluconazol (Difucan)-resistant strains. This is especially relevant given that opportunistic Candida can cause severe systemic infections. Tea Tree The oil has beneficial medical properties including antiseptic, antifungal and antibacterial, actions. Tea tree oil has been used topically against Staph including MRSA. Lavender Essential oil of lavender has antiseptic and anti-inflammatory properties. It was even used to disinfect hospitals during WWI. Lavender oil is extensively used for various respiratory infections, and has a calming effect on the nervous system. Galbanum Mentioned in the Old Testament, as well as by Hippocrates, Galbanum has one of the oldest recorded histories of beneficial use. It is both antimicrobial and anti-parasitic and is traditionally used for healing wounds and in the treatment of infection both internally and externally. Thymol from Oregano is a top pick for all kinds of infections. Tea Tree and Lavender are well known for topical use, and in very small quantities may be used internally. One of my pet essential oil ingredients is Galbanum, an ancient remedy favored by Hippocrates for infection.

37 Detoxification Pathway Support
Removes Toxins and Decreases Herxheimer Reactions, Supports Removal of Biofilms Dandelion Although maligned as a lowly weed, dandelion has numerous cleansing properties. It supports the liver and kidneys and is a diuretic, allowing toxins to be eliminated. The fresh juice may be applied directly to wounds The leaves are high in minerals and vitamins. Uva Ursi A useful diuretic and antimicrobial, Uva Ursi contains plant tannins that assist in removal of biofilm related infections, and is often used to treat UTI. Bladderwrack A seaweed know for supporting thyroid function, Bladderwrack also contains Fucoidan, which may prevent adhesion of bacteria and viruses, also helping prevent biofilm colonies from developing. Opening the drainage pathways of the liver and kidneys is important to assist the removal of toxins and decrease die off reactions. Uva Ursi and Bladderwrack both assist in biofilm removal as well as act as diuretics.

38 Immune Modulators Increase Overall Immune System Activity, Rejuvenate and Invigorate the Action of Immune Cells. Shiitake Shiitake has numerous health benefits. Lymphokines, such as interferon and interleukin stimulate the defense system, increasing the number of phagocytes including macrophages and other immune fighters that attack cancer cells, bacteria, and viruses. Shiitake also has potent antibiotic effects against other organisms. Noni Noni juice is an ancient health beverage possessing immune stimulating, anticancer, antibacterial, anti-fungal, and anti-aging properties. Several phytochemicals have been isolated from noni fruit indicating potential anti-inflammatory activity. Noni contains various powerful antioxidants that prevent free radicals from damaging cells. Cordyceps The Cordyceps mushroom has a long history as medicinal fungi. The earliest clear record is a Tibetan medical text in the 15th Century outlining the tonic properties. Recent research has verified its’ unique healing capacity. By up-regulating the immune system, we give the body a better chance to fight infection and prevent recurrence. Use of immune modulators like Shiitake, Cordyceps and Noni provide both immune support and additional antibiotic properties. I am sure you have noticed by now that many of the botanicals on our formulations cover more than one base, supporting the immune ssystem while killing pathogens, or repairing irritated or inflammed tissues. The feedback I often get is that these formulas provide a simple, elegant approach to treating infection. Patient compliance is very high, and results are seen in a short time which is gratifying to practitioners and patients.

39 Antioxidants Quench Free Radicals
Powerful Extracts Increase Cellular Integrity and Prevent Oxidative Stress, Inflammation and Tissue Destruction. Bilberry Bilberries contain one if the highest levels of OPC’s and help formation of and strengthening of connective tissue and capillaries, and are used for ocular health. The anti-inflammatory properties have also been helpful GI Dysbiosis. Bilberries inhibit or kill fungi, bacteria, and protozoans. Grape Seed Extract Grape Seed Extract is another natural bioflavonoid which helps strengthen and protect cell membranes from oxidative damage. Catechins help reduce allergic responses by inhibiting enzymes involved in the formation of histamine. Raspberry The fruit is high in ellagic acid, a phenolic compound that may help prevent cancer and helps to stop biofilm formation. Raspberry leaves are known historically for the treatment of diarrhea. In addition, raspberry leaves can be used to treat wounds, ulcers, and dental infections. Antioxidant phenolics such as Bilberry, Grape Seed and Raspberry serve double duty, not only by preventing biofilm formation, but also reducing inflammation and heal damaged tissues. In Dysbiosis this is an important factor in restoring integrity of the GI tract.

40 Clinical Goals Review:
Eliminate GI Dysbiosis due to pathogenic bacteria, yeast, fungus and parasites. Address biofilms and systemic infections, reduce LPS, and LTA translocation Eliminate allergens from the diet. Support detoxification: liver and toxic metals, LPS burden Raise antioxidants such as glutathione. Support beneficial organisms with pre and probiotics. Heal gut lining with Vit D-3, glutamine, other support supplements These are the fundamental protocols in any patient with chronic inflammation or any long term illness. As we have seen, Chronic inflammation is seen in myriad conditions including Diabetes, Heart Disease, Chronic Fatigue, Lyme disease, Neurological conditions, Depression, and virtually all Autoimmune Disorders,. These are caused or exaggerated by altered intestinal ecology due to diet and/or the presence of pathogens that alter intestinal permeability and create translocation of endotoxins such as LPS and LTA.

41 800.775.4140, 831.688.1533
We like to work with each new practitioner personally as you start to get familiar with the products, and so we can schedule a virtual in-service by computer or phone for you and your staff to answer questions about specific cases. Please fill out the form Karen has distributed, so that we can send you a copy of this presentation, and indicate if you would like to be contacted to set up a personal training. We are available at our table outside for any questions. I hope you have found this presentation informative, and thank you! Dr. Rachel Fresco L. Ac., Ph. D. , ©2014 Rachel Fresco. Reproduce with permission only. All Rights Reserved

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