Dr. Matthew E. Worth, DC, DACNB, FACFN

Transcription

1 Brain-Gut Connection Dr. Matthew E. Worth, DC, DACNB, FACFN Fellow, American College of Functional Neurology Diplomate, American College of Chiropractic Neurology Associate Professor of Clinical Neurology

2 The information enclosed in this lecture is protected by copyright. Unauthorized use, reproduction, or distribution of any portion of this presentation without written consent of the author is prohibited by law. Violator will be prosecuted.

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4 The digestive tract is an important component of the body s immune system. If fact, the intestines possesses the largest mass of lymphoid tissues in the human body. GALT is made up of several types of lymphoid tissue that stores immune cells (T/B lymphocytes) that carry out attacks and defend against pathogens.

5 GALT (Gastrointestinal Associated Lymphatic Tissue) Tonsils Adenoids Peyer s Patches Lymphoid aggregates in appendix & Large intestine Lymphoid tissue in stomach (age dependent) Small lymphoid aggregates in esophagus

6 (Dysbiosis) aka Leaky Gut Syndrome Over the last 5 years there has been an overwhelming amount of evidence-based studies accumulating that dysbiosis is a real condition that affects the lining of the intestines. The theory is that dysbiosis (increased intestinal permeability), is the result of damage to the intestinal lining, making it less able to protect the internal environment, as well as to filter needed nutrients and other biological substances.

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8 As a consequence, some bacteria and their toxins, incompletely digested proteins and fats, and waste not normally absorbed may "leak through the intestinal barrier" out of the intestines into the blood stream. This triggers an autoimmune reaction, which can lead to: Auto Immune Ds: Lupus (SLE) Crohn's disease Arthritis / RA MS Celiac Ds Autism Skin lesions: Eczema Acne Psoriasis Digestive disorders: Acid reflux chronic giardiasis Food allergies Chronic intestinal candidosis IBS, Bloating, constipation Dysautonomia: Headaches / migraines Raynaud's disease Behavioral, cognitive, attention changes

9 Association between Neural Antibodies and Different Neuroautoimmune Disorders Antigens Myelin Basic Protein (MBP) Myelin Oligodendrocyte Glycoprotein (MOG) a-b-crystallin Transaldolase Myelin Associated Glycoprotein (MAG GM 1, LM 1, GD 1b, GQ 1b ) Sulfatide Campylobacter Jejuni Sulfatide and Chondroitin Sulfate Glutamate Receptors Ion Channel Cerebellar Purkinje Cells MBP Neuron-Axon Filament Protein (NFP) Glial Fibrillary Acidic Protein (GFAP) Tubulin S-100 Ptotein, NFP, GFAP Muscarinic Acetylcholine Receptor Acetylcholine Receptor Multiple Sclerosis Disease Occurences Demyelinating Sensorimotor Neuropathies Guillain-Barre Syndrome Chronic Sensory Neuropathy Amyotrophic Lateral Sclerosis Or Lou Gehrig s Disease Rassmussen s Encephalitis Paraneoplastic Cerebellar Degeneration Neurotoxicity, Autism Alzheimer s, Brain Aging & Vascular Dementia Schizophrenia Myasthenia Gravis 9

10 The Damaged Brain What to consider

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12 Pathways involved in bidirectional communication between the gut microbiota and the brain. Multiple potential direct and indirect pathways exist through which the gut microbiota can modulate the gut brain axis. endocrine (cortisol) immune (cytokines) neural (vagus and enteric nervous system) pathways. The brain recruits these same mechanisms to influence the composition of the gut microbiota, for example, under conditions of stress. The hypothalamus pituitary adrenal axis regulates cortisol secretion, and cortisol can affect immune cells (including cytokine secretion) both locally in the gut and systemically. Cortisol can also alter gut permeability and barrier function, and change gut microbiota composition. Conversely, the gut microbiota and probiotic agents can alter the levels of circulating cytokines, and this can have a marked effect on brain function.

13 MUCOSAL IMMUNE ABNORMALITIES IMBALANCED GUT FLORA INTESTINAL BARRIER DYSFUNCTION SYSTEMIC INFLAMMATION NEUROINFLAMMATION NEUROINVASION NEURODEGENERATION From mucosal immune abnormalities to neuroinflammation and neurodegeneration. 13

14 What is Autoimmunity? Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response Is termed an autoimmune disease.

15 Proposed scheme of the induction by environmental factors of mucosal immune dysregulation and the production of inflammatory cytokines Vojdani A. ecam; advance access July 21, 2009, doi: /ecam/nep063.

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18 Stress copyright Aristo Vojdani, Ph.D., M.Sc., C.L.S. 18

19 From Vojdani A, et al. The immunology of immediate and delayed hypersensitivity reaction to gluten. Eur Jf Inflamm; 6(1):1-10,

20 Hidden Sources of Gluten Soy sauce Food starches Food emulsifiers Food stabilizers Artificial food coloring Malt extract, flavor, syrup Dextrin

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22 Gluten Sensitivity vs. Celiac Disease Celiac Disease Antigliadin Antibodies + HLA DQ + Transglutaminase + Small Intestine Biopsy + Endomysial Antibodies + Fecal Fat Microscopy + Gluten Sensitivity Antigliadin Antibodies + HLA DQ + Transglutaminase - Small Intestine Biopsy - Endomysial Antibodies - Fecal Fat Microscopy -

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24 WHITE BLOOD CELL CLASSIFACTION BREAKDOWN Neutrophils Monocytes (Macrophages) Basophils Eosinophils Lymphocytes Natural Killer Cells T-Cells B-Cells Cytotoxic T-Cells T-Suppresser T-Helper Regulatory T Cells BLOOD-BRAIN BARRIER Myeloid Progenitor Cells Microglia 24

25 VI. CD4 + T helper Subsets Th1/Th2 Cytokine Bias CD4+ T helper cells can be divided into subsets based on their cytokine production. T h 1 cells produce IL-2, IFN-g, TNF-b CKs which activate cell mediated immunity T h 2 cells activate IL-4, IL-6, IL-10 CKs that activate humoral immunity These Th subsets were originally identified using mouse T cell clones.

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27 copyright Aristo Vojdani, Ph.D., M.Sc., C.L.S.

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31 Brain-Blood Barrier Degrade Elevated Homocysteine Increased Oxidative Stress Physiological Stress Response HPA Axis Dysregulation Alcohol Glycosylated End Products Enhance Methylation Physiology Modulate Stress Physiology HPA Axis Regulation Alpha-Lipoic Acid Glutathione Antioxidants Brain Neuronal Activity Prostaglandin Balance 31

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