Inflammation: How to Cool the Fire Inside your Gut? REINVENTING DIAGNOSTICS

Inflammation: How to Cool the Fire Inside your Gut? REINVENTING DIAGNOSTICS

Future of Healthcare

REINVENTING DIAGNOSTICS

Inflammation

Gut Inflammation

Basis of a Healthy Immune System inhibiting immune system Nutrition Age, Stress, Alcohol, Allergen, Pathogen Sport, Water, Nutrition, Relaxation, (medicinal) Herbs Nutrition stimulating immune system

Food as Immunomodulator!? Food Allergy vs. Food Intolerance - genetic / exposure related - food allergen (protein) - antigen-presenting cell, T- & B lymphocytes IgE release - acute reaction - genetic / exposure related - food substances (e.g. herbs, chemicals) - non-specific activation of innate immune cells (via DAMPs, PAMPs) - metabolic activation of innate immune cells (e.g. STAMP2) inflammation cascade - delayed reaction - specific / adaptive immunity - non-specific / innate immunity

2 Branches of the Immune System Innate / Unspecific Immunity Adaptive / Specific Immunity Glenn Dranoff. Cytokines in cancer pathogenesis and cancer therapy Nature Reviews Cancer 4, 11-22 (2004) - self vs. non-self & danger vs. non-danger [2, 3] - Cellular host defense without memory - Phagocytosis and inflammation - Increased specifity - Acquired defense with memory - Antigen-presenting cells - Antibody production

The Immune System at the Front Line Immunomodulators Exogenic Factors PAMPs pathogen associated molecular pattern e.g. Bacteria, Viruses, Fungi Endogenic Factors DAMPs danger associated molecular pattern e.g. Nucleic Acids, Heat Shock Proteins Triggered by, e.g. UV radiation, mechanical irritation & food from infected, dead, injured or stressed non-apoptotic cells [3] release of endogenic molecules

Neutrophils and Immune Defense 1. PAMP 2. DAMP PRR Inflammatory cascade Neutrophil Macrophages, Endothelial Cells pro-inflammatory cytokines reactive oxygen species (ROS) lytic enzymes acute inflammation neutralize particle Pattern Recognition Receptors Occurrence Example Membrane-Bound Various host and immune cells Toll-Like Receptor (TLR), C-Type Lectin Receptor PAMP Cytosolic Soluble Cytoplasma of different host and immune cells Circulating freely in the blood NOD I-Like Receptor (NLR), RIG I-Like Receptor (RLR) Mannose-Binding Lectin (MBL), Surfactant-Protein A DAMP

What do Type II diabetes, atherosclerosis & intestinal autoinflammatory diseases have in common? the inflammasome - multiprotein complex e.g. in macrophages & neutrophils - assembly triggered by particles emerged during infection (e.g. LPS) tissue damage (e.g. ROS) or metabolic imbalances (e.g. uric acid crystal, glucose) [26] - regulating effect on gastrointestinal infections of the intestinal mucosa

Inflammasome - cytosolic PRR NLR (e.g. NLRP3, NLRP6) activation inflammatory protease Caspase-1 processsing pro-il-18 & pro-il-1β inflammatory, programmed cell death Pyroptosis release of pro-inflammatory cytokines

Trigger Immune Cells PRR Inflammasome Inflammatory Cascade Burst Continous Inflammation Chronic Inflammation

- abnormal inflammasome activation (associated with at least 30 disorders) disrupt intestinal homeostasis & promote auto-inflammatory diseases - Inflammasome regulation affects intestinal homeostasis & other organ systems, e.g. liver - Metabolic syndrome associated with: atherosclerosis, obesity, Type II diabetes

Food Intolerance: Potential Factors

Identify Triggers Food & Additives: activation innate immune system inflammation complex chronic conditions preterm aging... individual reactive substance Identification & elimination of food (substances), which may act as triggers for non-specific immune defense

Testing Food effectively Type I Food Allergy Mechanisms of the specific immune system Diagnose: detection of allergy triggering IgE antibodies: Radioactivity-based assays: RAST, RIST Non-radioactive assay: FEIA, EIA, ImmunoCap Test

Food Intolerance 1. Enzymatic or genetic induced sensitivities (e.g. lactase deficiency, celiac disease) Diagnose: e.g. hydrogen breath test, small intestine biopsy, GHP (Gut Health Profile) NOTE: - specific IgG titers do not necessarily indicate a food sensitivity - indicate an exposure to specific food particles - IgG may be a marker for food tolerance, not intolerance [33-35]

Blood Test that can SAVE YOUR LIFE C-Reactive Protein

Inflammation and Cardiovascular Disease: Is Abdominal Obesity the Missing Link? TNF- IL-6 CRP?? Adipose Tissue? Atherogenic, insulin resistant dysmetabolic milieu Risk of acute coronary syndrome Després JP. Int J Obes Relat Metab Disord. 2003;27:S22-S24.

Causes of Leaky Gut?

1 Low Fiber High Sugar Processed Food

2 Overuse of Medications

3 Low Grade Bug Imbalance

4 Poor Digestive Enzyme Function

5 Stress

6 Hormone Imbalance

Leptin TNF-alpha IL-6 PAI-1 Resistine Adiponectin

How do we Fix the Gut?

Eliminate the Cause

Eliminate the Cause Eat Right

Eat Right

Eliminate the Cause Eat Right Heal & Repair your Gut

Eliminate the Cause Eat Right Heal & Repair your Gut Optimize Healthy Bacteria

The 3 Most Important Probiotic Strains Lactobacillus Acidophilus DDS-1 Bifidobacterium Lactis Bifidobacterium Longum

Eliminate the Cause Eat Right Heal & Repair your Gut Optimize Healthy Bacteria Reduce Stress

Good sleep Decrease Cortisol Increase Leptin Melatonin Growth hormone

Get Active Brisk Walking 30 min per day for fitness 45-60 min per day for weight loss Weight Training Burn calories Increase metabolism Boost testosterone and DHEA Burn fats/ build muscle mass

Hormone Balance Strategy High Insulin- High protein diet, Exercise High Cortisol- Sleep enough, Eat right (mini meals), Reduce stress High Estrogen- Green tea, turmeric, flax and chia seeds, indole 3-carbinol Low Testosterone- Zinc, weight training, high protein diet Low DHEA- DHEA 5-25 mg daily with meals, Relora herbal supplement

Laboratory Hormone Assessment C-Reactive Protein Lab assessment of adrenal hormones- Cortisol and DHEA Measure Androgen levels- Testosterone Test for changes in sex hormones- Estrogen Test for Insulin Resistance and glucose dysregulation

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