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 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 10-14 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 gutderived inflammation is a novel pathway in CFS. LPS, Zonulin and Systemic Inflammation: Intestinal Dysbiosis and Leaky Gut Syndrome Clinical Goals: ① Eliminate GI Dysbiosis due to pathogenic bacteria, yeast, fungus and parasites. ② Address biofilms and systemic infections, reduce LPS, LTA translocation ③ Eliminate allergens from the diet. ④ Support detoxification: liver and toxic metals, LPS burden ⑤ Raise antioxidants such as glutathione. ⑥ Support beneficial organisms with pre and probiotics. ⑦ 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. 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 Antibiotics known to cause C. Difficile: Clindamycin Ampicillin Amoxicillin Cephalosporins Occasionally cause C. Difficile: Penicillin Erythromycin Ciprofloxacin 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 24 hour Exposure to Botanical Combination 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 Essential Oils: Prevention Adhesion and Disrupting or Destroying Biofilm Components 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. 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. 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). 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. 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. 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. 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 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 Text Text 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. 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. 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, anticancer 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. 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. 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. 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. 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. Clinical Goals Review: ① Eliminate GI Dysbiosis due to pathogenic bacteria, yeast, fungus and parasites. ② Address biofilms and systemic infections, reduce LPS, and LTA translocation ③ Eliminate allergens from the diet. ④ Support detoxification: liver and toxic metals, LPS burden ⑤ Raise antioxidants such as glutathione. ⑥ Support beneficial organisms with pre and probiotics. ⑦ 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. ©2014 Rachel Fresco. Reproduce with permission only. All Rights Reserved