Study Guide and Exercises for Human Microbiome and Dysbiosis in Clinical Disease An Integrative Functional Medicine approach to Understanding and Treating Microbial Imbalances and Chronic Infections Peer-Reviewed Monograph for Continuing Education Program • Volume 1: Parts 1 - 4 Alex Vasquez D.C. N.D. D.O. F.A.C.N. Peer-reviewed and distributed by International College of Human Nutrition & Functional Medicine ICHNFM.ORG www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 2 These questions are printed within the book as engagement exercises for the reader but are not included in the "final exam" (multiple choice pre-test and post-test) because they are open-ended, short-answer / essay questions: Active learning and reflection Dysbiosis—definition: Dysbiosis subtypes (based on location)—name each location following each of the prompts: 1. SR: 2. OD: 3. GI: 4. GU: 5. Derm: 6. P/T/B: 7. Env: Multifocal dysbiosis—definition: Polydysbiosis—definition: Combinatorial dysbiosis—definition: Microbial molecules, mechanisms, morphology—describe mechanisms/consequences of each: 1. Gram-negative bacterial products, LPS: 2. Gram-positive bacterial products: 3. L-form, pleomorphic, "cell wall-deficient" bacteria: 4. Immunostimulation by bacterial DNA, viral DNA and bacteriophage DNA: 5. Superantigens: 6. Antimetabolites: a) D-lactate: b) H2S: c) Propionic acid: d) Ammonia: e) P-cresol: f) HPHPA: 7. Beneficial metabolites and molecular signatures—name at least one: www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 3 Use the space below to discuss a few of the clinical implications of each of the following, as if you were explaining dysbiosis to a medical student or educated patient: 1. Gram-negative bacterial products, LPS 2. Gram-positive bacterial products 3. L-form, pleomorphic, "cell wall-deficient" bacteria 4. Immunostimulation by bacterial DNA, viral DNA and bacteriophage DNA 5. Superantigens 6. Antimetabolites 7. Beneficial metabolites and molecular signatures—note that these are generally anti-inflammatory Use the space below to list the pathophysiologic mechanisms of dysbiosis as reviewed in the book: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 4 Use the space below to describe—in narrative format— to an educated patient or professional colleague how bacteria can contribute to non-infectious metabolic/inflammatory disease: Auto-brewery syndrome Syndromes of pain, fatigue, depression Dysbiotic arthropathy, dysbiotic dermatitis, dysbiotic vasculitis Reactive arthritis (ReA) Diabetes, insulin resistance via systemic inflammation Name at least eight interventions for gastrointestinal dysbiosis (e.g., SIBO) that can be implemented with a low threshold for use due to excellent safety and effectiveness; write the dose/administration for each: Treatment Dose, Frequency Duration Contraindications/Cautions 1. 2. 3. 4. 5. 6. 7. 8. Name the various types of gastrointestinal dysbiosis and provide distinguishing features: 1. 2. 3. 4. 5. 6. 7. 8. Name the various clinical conditions associated with or known to be caused (in large part) by gastrointestinal dysbiosis: www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 5 Name the treatments that are safe and effective enough to justify a low threshold of use for a patient suspected of having SIBO on the first day of treatment without confirmatory/laboratory/objective testing; also, name the two most studied botanical medicines for gastrointestinal dysbiosis along with their dosage and duration: • Diet and nutrition: • Botanicals: • Safe/nonabsorbed antimicrobial agents: • Additional treatments: How does hypothyroidism contribute to SIBO? How is hypothyroidism assessed and treated? • History (at least 6 items): • Physical exam (at least 3 objective findings that are specific to hypothyroidism): • Laboratory (name the 6 lab tests): • Empiric treatment and response to treatment (define treatment and dosages—give 3 prescription options): • Contraindications to treatment with thyroid hormone: Name the signs and symptoms of mild "subclinical" gingivitis: Name at least 10 treatments for gingivitis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Given that "sensitive teeth" and/or gums that bleed when flossed or provoked are indications of gum disease and the resultant odontogenic inflammation and bacterial translocation and endotoxemia, write your plan for assessing this in your patients and managing the problem clinically: www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 6 Given that chronic sinusitis is common and is associated with an exaggerated immune response to benign bacteria/fungi, name at least two examples of interventions for each of the following 3 categories of treatments against sinus dysbiosis: • Antimicrobial: • Immunorestorative: • Tolerogenic: Name 4 microbes involved in genitourinary/urogenital dysbiosis: 1. 2. 3. 4. Name 4 treatments against genitourinary/urogenital dysbiosis: 1. 2. 3. 4. Name 5 treatments for cutaneous/dermal dysbiosis and instructions for implementation: 1. 2. 3. 4. 5. www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 7 Pathophysiologic responses—describe mechanisms/consequences of each: 1. Damage to the intestinal mucosa—what is the cause, and what is the effect? What is zonulin, and what two specific items trigger its release? 2. Activation of inflammatory pathways—define each and name one agonist: a) Toll-like receptors (TLR): b) NFkB: c) DAMP: d) PAMP: e) Inflammasome: 3. Mitochondrial hyperpolarization—name 1 cause and 1 consequence: mTOR activation—name 1 cause and 1 consequence: 4. Molecular mimicry, cross-reactivity—give 2 examples of diseases with the associated microbes/molecules: 5. Enhanced presentation of autoantigens—name 1 trigger: 6. Bystander activation—name 1 trigger: 7. Haptenization and the formation of neoautoantigens—name the classic disease association: 8. Immune complex formation and deposition—name 3 conditions: 9. Microbial allergy, hypersensitivity—name 3 conditions: 10. Insufficiency dysbiosis—name 3 consequences: 11. Inhibition of detoxification—name one cause beyond genetics/SNP and medications: 12. Vitamin D metabolism and reception—name the two human antimicrobial peptides: 13. Bacterial and fungal proteases impair immune defenses—what is the consequence of IgA protease? 14. Immunosuppression, gliotoxins—name one microbe that produces local immunosuppression: 15. Mold toxins—mycotoxins—name two treatments for environmental toxin exposure: 16. Biofilms—how are dental biofilms removed? 17. What causes impairment of mucosal digestion? Name 2 causes and 1 consquence: 18. What is central sensitization? Name 2 causes and 1 consquence of glial activation: 19. Dysbiosis-induced endocrine dysfunction—which 3 hormones are elevated? Which 3 are suppressed? 20. Microbe-induced epigenetic changes—what are "HERVs"? www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 8 Prototypic clinical manifestations: 1. Autointoxication, auto-brewery syndrome, encephalopathy: a) Evaluations: b) Treatments: 2. Syndromes of pain, fatigue, depression (e.g., fibromyalgia) caused by dysbiosis: a) Evaluations: b) Treatments: c) Name one microbial molecule that can cause mitochondrial dysfunction and glial activation: 3. Dysbiotic arthropathy, dermatitis, vasculitis a) Evaluations: b) Treatments: c) What are immune complexes, and what are the clinical consequences? 4. Reactive arthritis a) Evaluations: b) Treatments: c) Name two microbes that share amino acid homology with HLA-B27: www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease 9 Copyrights:  2004-2015 by Alex Vasquez. All rights reserved by the author and enforced to the full extent of legal and financial consequences internationally. No part of this book may be reproduced, stored in a retrieval system, used for the creation of derivative works, or transmitted by any means (electronic, mechanical, photocopying, recording, or otherwise) without written permission from the author. Trademarks: ® 2013-present by Alex Vasquez. The functional immunology/inflammology protocol discussed in this series of videos/notes/books/audios is recalled by the F.I.N.D.S.E.X. acronym trademarked™ in association with Dr Vasquez’s books and videos including but not limited to Functional Immunology and Nutritional Immunomodulation (2012), F.I.N.D. S.E.X. The Easily Remembered Acronym for the Functional Inflammology Protocol (2013), Integrative Rheumatology and Inflammation Mastery, 3rd Edition (2014). Portland, Oregon; Integrative and Biological Medicine Research and Consulting, LLC. All rights reserved and enforced. For additional information and resources, see InflammationMastery.com and/or FunctionalInflammology.com. Of note, additional trademarks referenced/cited in this work include International College of Human Nutrition and Functional Medicine®, International Conference on Human Nutrition and Functional Medicine®, and International Journal of Human Nutrition and Functional Medicine® in Spain. Notices: The intended audiences for this book are health science students and doctorate-level licensed medical clinicians. This book has been written with every intention to make it as accurate as possible, and each section has undergone peerreview by an interdisciplinary group of clinicians. In view of the possibility of human error and as well as ongoing discoveries in the biomedical sciences, neither the author nor any party associated in any way with this text warrants that this text is perfect, accurate, or complete in every way, and all disclaim responsibility for harm or loss associated with the application of the material herein. Information and treatments applicable to a specific condition may not be appropriate for or applicable to a specific patient; this is especially true for patients with multiple comorbidities and those taking pharmaceutical medications, which are generally associated with multiple adverse effects and drug/nutrient/herb interactions. Given that this book is available on an open market, lay persons who read this material should discuss the information with a licensed medical provider before implementing any treatments and interventions described herein. Textbooks in this series—past, current, and forthcoming 1. Volume 1: Functional Inflammology: Introduction to Clinical Nutrition, Functional Medicine, and Integrative Pain Management for Disorders of Sustained Inflammation 2. Volume 2: Disorders of Metabolic Inflammation: Hypertension, Diabetes, Fibromyalgia, Migraine, Alzheimer's disease, Parkinson's disease, etc 3. Volume 3: Disorders of Allergic Inflammation: General Allergy, Atopic Dermatitis, Asthma, etc 4. Volume 4—most recently published in 2014 as Naturopathic Rheumatology v3.5 with the rheumatology-specific section (companion to volume 1) published as Functional Medicine Rheumatology v3.5: Disorders of Autoimmune Inflammation / Integrative Rheumatology: Psoriasis, Rheumatoid Arthritis, SLE, MS, Vasculitis, Dermatomyositis, etc 5. Volume 5: Clinical Mastery of Common Musculoskeletal Disorders: Integrative Orthopedics www.ICHNFM.ORG Human Microbiome and Dysbiosis in Clinical Disease Date & Notes Started in 2004, updated 2014 Earlier versions: 2009, 2011, 2012 Earlier versions: 2005, 2009 Earlier versions: 2006, 2007, 2014 Earlier versions: 2004, 2007, 2012 10