Brain-Gut Connection - Dr. Matthew E. Worth, DC, DACNB, FACFN Fellow, American College of Functional Neurology

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

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• 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.

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

(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.

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:              • Digestive disorders:
    • Lupus (SLE)                   • Acid reflux
    • Crohn's disease               • chronic giardiasis
    • Arthritis / RA                • Food allergies
    • MS                            • Chronic intestinal candidosis
    • Celiac Ds                     • IBS, Bloating, constipation
    • Autism                   • Dysautonomia:
• Skin lesions:                     • Headaches / migraines
    • Eczema                        • Raynaud's disease
    • Acne                     • Behavioral, cognitive, attention
    • Psoriasis                    changes

Association between Neural Antibodies and Different Neuroautoimmune Disorders
                 Antigens                             Disease Occurences
Myelin Basic Protein (MBP)                Multiple Sclerosis
Myelin Oligodendrocyte Glycoprotein (MOG)
a-B-Crystallin
Transaldolase
Myelin Associated Glycoprotein             Demyelinating Sensorimotor Neuropathies
 (MAG – GM1, LM1, GD1b, GQ1b)
Sulfatide
Campylobacter Jejuni                       Guillain-Barre Syndrome
Sulfatide and Chondroitin Sulfate          Chronic Sensory Neuropathy
Glutamate Receptors                        Amyotrophic Lateral Sclerosis
                                            Or Lou Gehrig’s Disease
Ion Channel                                Rassmussen’s Encephalitis
Cerebellar Purkinje Cells                  Paraneoplastic Cerebellar Degeneration
MBP                                        Neurotoxicity, Autism
Neuron-Axon Filament Protein (NFP)
Glial Fibrillary Acidic Protein (GFAP)
Tubulin
S-100 Ptotein, NFP, GFAP                   Alzheimer’s, Brain Aging & Vascular
                                            Dementia
Muscarinic Acetylcholine Receptor          Schizophrenia
Acetylcholine Receptor                     Myasthenia Gravis
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The Damaged Brain
 What to consider

.

• 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.

MUCOSAL IMMUNE ABNORMALITIES

        IMBALANCED GUT FLORA

              INTESTINAL BARRIER DYSFUNCTION

                     SYSTEMIC INFLAMMATION

                           NEUROINFLAMMATION

                                 NEUROINVASION

                                        NEURODEGENERATION

From mucosal immune abnormalities to neuroinflammation and neurodegeneration.
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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.

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:10.1093/ecam/nep063.

Stress

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

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From Vojdani A, et al. The
immunology of immediate
and delayed hypersensitivity
reaction to gluten. Eur Jf
Inflamm; 6(1):1-10, 200

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Hidden Sources of Gluten

•   Soy sauce
•   Food starches
•   Food emulsifiers
•   Food stabilizers
•   Artificial food coloring
•   Malt extract, flavor, syrup
•   Dextrin

Gluten Sensitivity vs. Celiac Disease

Celiac Disease                 Gluten Sensitivity
•   Antigliadin Antibodies +   •   Antigliadin Antibodies +
•   HLA–DQ +                   •   HLA–DQ +
•   Transglutaminase +         •   Transglutaminase -
•   Small Intestine Biopsy +   •   Small Intestine Biopsy -
•   Endomysial Antibodies +    •   Endomysial Antibodies -
•   Fecal Fat Microscopy +     •   Fecal Fat Microscopy -

Kharrazian

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WHITE BLOOD CELL CLASSIFACTION
                          BREAKDOWN

     Neutrophils
     Monocytes (Macrophages)
     Basophils
     Eosinophils
     Lymphocytes                            Natural Killer Cells

                       B-Cells
      T-Cells

                                 Cytotoxic T-Cells

                     T-Suppresser

                Regulatory T Cells
     T-Helper

---------------------- -----------BLOOD-BRAIN BARRIER-----------------------------------
Myeloid Progenitor Cells                          Microglia24

VI. CD4+ T helper Subsets
              Th1/Th2 Cytokine Bias

• CD4+ Thelper cells can be divided into subsets
  based on their cytokine production.

• Th1 cells produce IL-2, IFN-g, TNF-b CKs
  which activate cell mediated immunity

• Th2 cells activate IL-4, IL-6, IL-10
  CKs that activate humoral immunity
 These Th subsets were originally identified using mouse T cell clones.

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

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Brain-Blood Barrier

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

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