Role of Gut Ecosystem inAutoimmune Disorders

Week 5

Today Inflammation and role of mitochondria Autoimmunity How is gut health related to

autoimmunity Fecal Transplant Case studies

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

What threatens themicrobiome 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

Gut microbiota based on diet and disease

Ref: David et al, 2013. Nature

How does microbiome getaffected? 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

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

What is Acute Inflammation Inflammare- “to set

on fire” Goals

Eliminate cause Remove necrotic

cells/tissues Initiate repair

Acute inflammationis triggered by acause Quick and temporary

Redness, swelling,heat, pain

Goes away

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

Birth of Immunology Elie Metchnikoff Phagocytosis Immune system

70-80% in gut protects from

infections, toxins,allergens

Keeps track offoreign substances

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”

Chronic Inflammation

Repeated threats -> Overactive immune system

Ref: Robbins Basic Pathology 9th ed.

Acute vs. ChronicInflammation

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

Mitochondria in health anddisease

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

Oxidative stress &Mitochondria Mitochondria use oxygen to release

energy Free radicals are generated-

programmed cell death is necessary! Inflammation ->Impaired mitochondria -

> cellular suicide -> destruction ofneurons

What is Autoimmunity Constant presence of

invaders Immune system attacks

constantly Attacks its own tissues Some foreign invaders

resemble body’s tissuesand antigens are madein response

Autoimmune disorders Triggers

Antibiotics Toxins Food Lifestyle Hormonal imbalance Stress

How? Free Radicals Leaky gut Microbiome and gut

repair Neurotransmitter

through gut brainaxis

Hormonal disbalance

Common AutoimmuneDisorders Intestine:

Crohn’s disease: abnormal E.coli Celiac-intestine

Pancreas Type 1 diabetes

Systemic Rheumatoid Arthritis Lupus- systemic

Nerves Multiple Sclerosis

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

Repeated doses of Antibiotics

Ref: Dethlefsen et al 2010, PNAS

Antibiotic Resistance

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

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

How does age changemicrobiota? 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

Microbiome changes with age

Sugar as a Trigger

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

GMOs as triggers GMOs are created to resist pests and infections by enhancing

plants’ digestive enzyme inhibitors and pro-inflammatorymolecules

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: https://www.youtube.com/watch?t=17&v=AQMlPYkngXY Seeds of Death full movie:

https://www.youtube.com/watch?v=a6OxbpLwEjQ Monsanto gets owned by 11yr old boy- TEDx:

https://www.youtube.com/watch?v=SvVZwJbs54c

Why avoid GMOs American Academy of Environmental Medicine

(AAEM) warns that “it is biologically plausible forGenetically Modified Foods to cause adverse healtheffects in humans.”

Contain more pesticides than non-GMOs Pesticides lead to leaky gut Leaky gut causes gut dysbiosis Organic vs regular meat:

http://www.drperlmutter.com/dangerous-meat-dairy/ Learn More: www.responsibletechnology.org www.autoimmunesummit.com

Inducers of ChronicInflammationAllergens

Sugar Trans fats Corn Soy Dairy Meat Preservatives Alcohol Gluten

Antibiotics Antacids Age Stress Exercise Bacterial and Yeast

overgrowth

Gut Health and Autoimmunity

Leaky gut and Autoimmunity

Leaky gut to Autoimmune

Inflammation and Brain Sore brain?

Depression Dementia Alzheimer’s Memory Autism

Autism to Alzheimer’s : “same diseaseshowing up at different ends of agespectrum”

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 coreissues in autism such as what changes in the brain to produce the behaviors welabel as “autistic.”

1. Why are so many children frequently or chronically sick2. Why are so many people chronically sick3. The growing challenges to the health of people’s brains4. Global crisis of “serious compromises to our food supply”; toxins5. State of our planet inundated with challenges to its integrity

Autism Revolution: “autism is something that develops and is generated by thebrain micromoment by micromoment — that is, it is a PROCESS, not ahardwired fixed thing. It is also something that can potentially be unwound, atleast to the point of getting rid of surplus obstructions to function”-www.marthaherbert.org. www.autismrevolution.org

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 thebrain”- Dr. Herbert

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 thechild was essentially seizure free

Prevention of Autism andrelated brain disordersReducing risks Food – avoid junk and processed food Toxins- avoid toxic exposures whenever possible Bugs – minimize infections exposures Stress – avoid excessive stimulation and overloadIncreasing 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 healthygut 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: http://www.autismwhyandhow.org/how-can-we-help/prevention/

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

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

Comparing Microbiomes

Ref: Nature, 25 March, 2015 http://www.nature.com/ncomms/2015/150325/ncomms7505/full/ncomms7505.htm

How we get off track?

What’s next in health? What does a healthy microbiome look

like? How can we replenish the gut for

healthy microbiome?

Getting back on track…

Ref: Salazar et al 2014. Frontiers in genetics: http://journal.frontiersin.org/article/10.3389/fgene.2014.00406/full

Cooling off inflammation Probiotics orally Prebiotic foods- fibre, fermented, plants, fats

Changing lifestyle factors Eliminating allergens Eliminating pathogens Probiotic enemas Fecal Transplant

Fecal Transplant 15 out of 16 patients with C.difficile were

cured with fecal transplant vs 3/15 withantibiotic 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 https://www.coursera.org/learn/microbiome/lecture/lvQLP/interview-on-location-in-

tanzania-with-jeff-leach

Video: https://www.youtube.com/watch?v=B9A7E08JoBs

Case Studies

Future of Treatments Dietary changes

lead to type ofbacterial population.

Treatment ofdiseases withspecific diets?

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

What to eliminate whenhealing 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

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