Role of Gut Ecosystem in Autoimmune Disorders. Week 5

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Julius Jacobs
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1 Role of Gut Ecosystem in Autoimmune Disorders Week 5

2 Today Inflammation and role of mitochondria Autoimmunity How is gut health related to autoimmunity Fecal Transplant Case studies

3 Microbiome in health 90% Bacterial cells in our body Gut lining and repair Digest food Provide nutrition Gut motility Brain health Gut brain axis neurotransmitters

4 What threatens the microbiome Food additives and junk/processed food Lack of adequate Sleep High and constant Stress Lack of relaxation Lack of movement Continuous medications/antibiotics Environmental toxins Sleep, Thoughts, Eating, Movement disruptions

5 Gut microbiota based on diet and disease

6 Ref: David et al, Nature

7 How does microbiome get affected? Lack of diversity Low ratio of healthy to pathogenic strains Colonies of symbiotic bacteria change Growth of yeast Gut environment changes in acid content and temperature

8 What happens in gut dysbiosis? Acid content changes Pathogens start increasing Oxidative stress/free radicals Cell membranes get disrupted Mitochondria start to die Leaky Gut Chronic Inflammation Autoimmunity

9 What is Acute Inflammation Inflammare- to set on fire Goals Eliminate cause Remove necrotic cells/tissues Initiate repair Acute inflammation is triggered by a cause Quick and temporary Redness, swelling, heat, pain Goes away

10 Steps in inflammation Vasodilation increased blood flow to area redness heat Increased permeability Loss of fluids from vessels concentration of red cells decreased blood flow Accumulation of immune cells

11 Birth of Immunology Elie Metchnikoff Phagocytosis Immune system 70-80% in gut protects from infections, toxins, allergens Keeps track of foreign substances

12 What is an allergy? An incorrect immune response Lack of exposure to variety of bacteria Delayed colonization of bacteria Bacteria in gut flip switches to correct immune responses at different ages Early exposure to antibiotics also leads to allergies Less Fermicutes and high proteobacteria are found in guts of allergic people A LITTLE DIRT NEVER HURT

13 Chronic Inflammation Repeated threats -> Overactive immune system

14 Acute vs. Chronic Inflammation Ref: Robbins Basic Pathology 9th ed.

15 Conditions with Chronic Inflammation Bone and Joint disorders Cancers of all types Cardiovascular diseases Digestive disorders Emotional and cognitive- Brain function Hormonal Metabolic Respiratory Skin conditions

16 Mitochondria in health and disease

17 Mitochondrial functions Mitochondria provide energy in packets Mitochondria have their own DNA This DNA affects the cellular DNA Mitochondria use carbs and oxygen Some cells can contain high amounts of mitochondria (upto 40% of the cell s mass) Only mother s mitochondria are inherited

18 Oxidative stress & Mitochondria Mitochondria use oxygen to release energy Free radicals are generatedprogrammed cell death is necessary! Inflammation ->Impaired mitochondria - > cellular suicide -> destruction of neurons

19 What is Autoimmunity Constant presence of invaders Immune system attacks constantly Attacks its own tissues Some foreign invaders resemble body s tissues and antigens are made in response

20 Autoimmune disorders Triggers How? Antibiotics Free Radicals Toxins Leaky gut Food Lifestyle Hormonal imbalance Stress Microbiome and gut repair Neurotransmitter through gut brain axis Hormonal disbalance

21 Common Autoimmune Disorders Intestine: Crohn s disease: abnormal E.coli Celiac-intestine Pancreas Type 1 diabetes Systemic Rheumatoid Arthritis Lupus- systemic Nerves Multiple Sclerosis

22 Antibiotics and Microbiota Antibiotics stop bacteria from Making proteins Growing Making cell walls Transporting nutrients Antibiotics make holes in cell membranes Antibiotics kill all bacteria, not just pathogens Reduce microbial diversity Antibiotic Resistance

23 Repeated doses of Antibiotics Ref: Dethlefsen et al 2010, PNAS

24 Antibiotic Resistance

25 Genetics and Inflammation Surrogate mice show similar microbiome compared to biological Environment is more important than genetics for gut microbiome Genes turn on or off based on environmental triggers Genetics does play some role

26 Microbiome depends on Age Genetics Environment Antibiotic use Hormone levels Immune system function Metabolism

27 How does age change microbiota? Infants start with low gut microbial diversity Changes each day depending on food and environment Microbial diversity and stability reduces with old age It is possible to control the microbiome changes STEM

28 Microbiome changes with age

30 Sugar as a Trigger

31 Sugar in Brain Carbohydrates break down to sugar Process of glycation -> sticky cells Excess sugar: Secretes excess insulin Promotes secretion of cortisol and adrenaline Converts to trans fat Produces inflammatory cytokines -> brain damage Diabetes type 2 has 4x risk of Alzheimer s Sugar triggers inflammation -> heart disease, obesity, cancer, diabetes, rapid aging

32 GMOs as triggers GMOs are created to resist pests and infections by enhancing plants digestive enzyme inhibitors and pro-inflammatory molecules GMOs can even resist extra pesticides Many GMOs have been tested for 3 months or less Are these modifications causing inflammatory secretions? Gut dysbiosis? Leaky gut? Who is doing the research? No federal regulations in North America Europe has strict regulations Videos: Seeds of Death full movie: Monsanto gets owned by 11yr old boy- TEDx:

33 Why avoid GMOs American Academy of Environmental Medicine (AAEM) warns that it is biologically plausible for Genetically Modified Foods to cause adverse health effects in humans. Contain more pesticides than non-gmos Pesticides lead to leaky gut Leaky gut causes gut dysbiosis Organic vs regular meat: Learn More:

34 Inducers of Chronic Inflammation Allergens Sugar Trans fats Corn Soy Dairy Meat Preservatives Alcohol Gluten Antibiotics Antacids Age Stress Exercise Bacterial and Yeast overgrowth

35 Gut Health and Autoimmunity

36 Leaky gut and Autoimmunity

37 Leaky gut to Autoimmune

38 Inflammation and Brain Sore brain? Depression Dementia Alzheimer s Memory Autism Autism to Alzheimer s : same disease showing up at different ends of age spectrum

39 Autism Martha Herbert, MD, PhD: I believe that this is the only way we will even be able to ask the right and most productive scientific questions about core issues in autism such as what changes in the brain to produce the behaviors we label as autistic. 1. Why are so many children frequently or chronically sick 2. Why are so many people chronically sick 3. The growing challenges to the health of people s brains 4. Global crisis of serious compromises to our food supply ; toxins 5. State of our planet inundated with challenges to its integrity Autism Revolution: autism is something that develops and is generated by the brain micromoment by micromoment that is, it is a PROCESS, not a hardwired fixed thing. It is also something that can potentially be unwound, at least to the point of getting rid of surplus obstructions to function -

40 Autism and gut 95% autistic children have GI challenges and swollen bellies Frequent infections and allergies Have had multiple courses of antibiotics 70% have altered immune function Gut, immune and toxicity issues are the starting point of what happens to the brain - Dr. Herbert

41 Treating Autism with Food Autism and Dietary Therapy: Case Report and Review of the Literature. Herbert and Buckley (2013): J. Child Neurology Child with autism and epilepsy Limited response to other interventions Remarkable improvement with gluten-free, casein-free diet After puberty: Additionally ketogenic diet: High fat with medium chain triglycerides Consumption of high amounts of vegetables Reduction in obesity, cognitive and behavioural features Autism rating scale score: from 49 to 17 over several years; intelligence quotient: 70 point increase: From Autistic to non-autistic 14 months after the initiation of the diet the child was essentially seizure free

42 Prevention of Autism and related brain disorders Reducing risks Food avoid junk and processed food Toxins- avoid toxic exposures whenever possible Bugs minimize infections exposures Stress avoid excessive stimulation and overload Increasing resiliency food optimize high nutrient density food Toxins keep the biological systems that handle toxin elimination as healthy as possible Bugs maintain the health and diversity of the gut microbes through high fibre, fermented foods, yogurt and kefir and/or probiotics because healthy gut flora support the immune system and many metabolic functions Build protections against stress: Increase maternal-infant and parent-child synchrony, sensitivity and quality of relationships develop sensory friendly environments Follow a sensory diet for an optimal level of stimulation Build skills so situations can be handle-able instead of overwhelming Support development of regulation and co-regulation Ref:

43 Depression Exercise and fish oil or antidepressants? Depression is low grade inflammation of the brain High levels of inflammatory cytokines Cytokines overactivate stress response Less serotonin Overactive immune system- chronic inflammation Depression linked with heart disease and autoimmune diseases Vagal nerve stimulation relieves depression

44 Treating Inflammation Treat the gut: reduce, eliminate, prevent chronic inflammation Food- mostly vegetarian Water Stress relief Adequate sleep Adequate exercise Eliminate allergens- sugar, gluten, dairy, meat Controlled use of antibiotics and medication (NSAIDs, Antacids etc) Treat yeast and pathogen overgrowth

45 Comparing Microbiomes Ref: Nature, 25 March,

46 How we get off track?

47 What s next in health? What does a healthy microbiome look like? How can we replenish the gut for healthy microbiome?

48 Getting back on track Ref: Salazar et al Frontiers in genetics:

49 Cooling off inflammation Probiotics orally Prebiotic foods- fibre, fermented, plants, fats Changing lifestyle factors Eliminating allergens Eliminating pathogens Probiotic enemas Fecal Transplant

50 Fecal Transplant 15 out of 16 patients with C.difficile were cured with fecal transplant vs 3/15 with antibiotic Bacteria compete with each other Jeff Leach: Human Food Project What differences will occur when moving to US Include high fibre diet is most imp Pay attention to your gut- everyone s different Men and women eat different foods- different microbiomes Video:

51 Case Studies

52 Future of Treatments Dietary changes lead to type of bacterial population. Treatment of diseases with specific diets?

53 Simplified cooking for Microbiome Health Steamed or sauteed vegetables Leafy greens: kale collards, chard, asian greens, lettuce Deep colours: berries, tomatoes, beets, carrots, winter squash Sulfur: broccoli, cabbage, asparagus, brussels, turnips High fibre: leeks, jicama, artichoke, celery, yam Baked fish, sardines Brown rice Whole grains in moderation Soups with sea weeds Lentils, legumes- in moderation or eliminate if treating inflammation Olives, nuts, coconuts, seeds, eggs, avocados, ghee, nut butters, grass-fed butters Fermented foods- sauerkraut, kefir, yogurt, kimchi, sprouts, pickles in brine not vinegar, mustard, horseradish, corned beef Portion control for meats and dairy 1-2 fruits Add turmeric, ginger, onions, garlic, herbs, vinegar Juices and smoothies in spring and summer Garlic, onions, mustards, sweet potatoes in fall Bitter greens in spring Soups, nuts, fish, meats, dark greens, mushrooms and roots in winter

54 What to eliminate when healing Grains/Gluten Legumes Sugar Artificial foods Packaged foods Alcohol/coffee Juices High sugar and sweet fruits Regular meats Dairy Eggs GMOs- canola oil, corn, soy, salmon, tomatoes, zucchini, yellow summer squash

55 Homework Revise previous weeks Find out if there is one change you would like to make in your food One change you would like to make in your lifestyle- sleep, exercise, stress relief Find out what comes in the way to making the change Get support Read: Autoimmune Solution, Amy Myers, MD

Stress Equation. Week 4

Stress Equation. Week 4 Stress Equation Week 4 So far Microbiome is affected by food and environment Microbiome affects the gut Gut affects the brain and immune system and each other Plant protein is more absorbable and complete