Dietary Approach to MS Microbiome and the

Gut Brain Immune Axis Dr. Terry Wahls

Departments of Internal Medicine/Neurology

The Wahls Institute, P.L.C.

Disclosures• Grant Funding –

– National MS Society

• Trademarks – Wahls™, Wahls Paleo™ , Wahls Paleo Plus™ Diet Plans, Wahls Protocol®

• Financial relationships with Penguin Random House Inc.; Integrative Medicine for Mental Health; Institute for Health and Healing; SuttlerPacific, BioCeuticals; NCURA; MCG Health Inc.; Genova Diagnostics

• Equity interest – Dr. Terry Wahls LLC – The Wahls Institute PLC– www.terrywahls.com

Books

Bach J-FCA. The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. New England Journal of Medicine. 2002;347(12):911-920.

The two routes by which diet can influence our health: (A) the metabolism of our cells and

(B) the population of our gut microbiota.

Paolo Riccio, and Rocco Rossano ASN Neuro 2015;7:1759091414568185Copyright © by SAGE Publications Inc, or the American Society for Neurochemistry, unless otherwise noted. Manuscript

content on this site is licensed under Creative Commons Licenses.

Total number of microbiome-related publications in PubMed by year

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Articles

Articles

Life Begins in the Ocean

6

By Tiago Fioreze -https://commons.wikimedia.org/w/index.php?curid=6111892

Life Timeline Billions of Years

Going back in time Billions of years • 4.5 Water • 4.0 Simple life • 3.0 Photosynthesis • 2.5 Oxygen crisis • 1.5 Mitochondria Multi-cellular• 0.5 (500 Million) Land plants/ animals • 0.2 (200 Million) Mammals • 0.00025 (250 Thousand) Humans• 0.00001 (10 Thousand) grains and legumes

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Our Human Ecosystem Began In The Ocean

© Dr. Terry Wahls LLC, All Rights Reserved. 8

By Tiago Fioreze -https://commons.wikimedia.org/w/index.php?curid=6111892

Guts Populated by Ocean Microbiome

• Co-operative mutualistic relationship

• We are all supra-organisms – as dependent on the microbes as our cells are upon our mitochondria to function

© Dr. Terry Wahls LLC, All Rights Reserved. 9

Our Gut Garden Evolved For Mutual Benefits

• Microbes divide every 20 minutes (1 billion years)– Billions of generations

• Humans every 25 years (250,000 years) – 10,000 generations

• We are all supra-organisms – as dependent on the flora in our gut as our cells are upon our mitochondria to function

© Dr. Terry Wahls LLC, All Rights Reserved. 10

Photo Copyright (c)

2004 Richard Ling.

Parasites or Symbionts

Helminth–host immunological interactions: prevention and control of immune-mediated

diseases

Ann N Y Acad Sci. 2012 Jan; 1247: 83–96.

Hymenolepis diminuta

Is eating behavior manipulated by the gastrointestinal microbiota?

• Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness.

© Dr. Terry Wahls LLC, All Rights Reserved. 14

Bioessays. 2014 Oct; 36(10): 940–949.

Gut Brain Immune Axis

• Gut microbiota influence the brain and immune system balance

• Diet influences the microbiome strongly

• Exercise, sleep, stress level also important

• Changes in the colon mucosa every early in the disease process

Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology? J Immunol Res. 2017;2017:790482The multiple sclerosis microbiome? Ann Transl Med. 2017 Feb;5(3):53.Microbiota-gut-brain axis and the central nervous system. Exp Mol Med. 2017 May 26;49(5):e339Microbiota-gut-brain axis and the central nervous system. Oncotarget. 2017 May 10Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med. 2017 May; 49(5): e340.Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol Neuroinflamm. 2017 Jun 14;4(4):e362.

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Microbiota in T-cell homeostasis and inflammatory diseasesExp Mol Med. 2017 May; 49(5): e340.

17Gut-CNS-Axis as Possibility to Modulate Inflammatory Disease Activity-Implications for Multiple Sclerosis Int J Mol Sci. 2017 Jul; 18(7): 1526.

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

Clin Ther. 2015 May 1;37(5):984-95.

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30, 31; ○) and in the United

States from 1975 to 2000 (32; ♦) is compared with obesity rates in the United States in non-

Hispanic white men aged 60–69 y (17; •).

Johnson R J et al. Am J Clin Nutr 2007;86:899-906

©2007 by American Society for Nutrition

Proc Natl Acad Sci U S A. 2015 Nov 17; 112(46): 14105–14112.

The composition of gut microbiota is influenced by multiple factors, such as diet and host genotype. Within the gut, ecological processes such as selection and evolution take place. The use of antibiotics reduces the numbers and diversity of gut microbiota.

van den Hoogen WJ1, Laman JD2, 't Hart BA2,3.Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota. Front Immunol. 2017; 8: 1081.

Carriage Carriage of microbial taxa varies while metabolic pathways remain stable within a healthy population of microbial taxa varies while

metabolic pathways remain stable within a healthy population

Nature. 2012 Jun 14; 486(7402): 207–214.

Diet rapidly and reproducibly alters the human gut microbiome.

© Dr. Terry Wahls LLC, All Rights Reserved. 26Nature. 2014 Jan 23; 505(7484): 559–563.

Microbes and Behavior

• Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness.

• Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness.

© Dr. Terry Wahls LLC, All Rights Reserved. 27

Is eating behavior manipulated by the gastrointestinal microbiota? Bioessays. 2014 Oct; 36(10): 940–949.

Microbiota and Mood

• Microbial community structures in the three healthy adults were strongly correlated with mood states (105 days).

• Bacterial genera Roseburia, Phascolarctobacterium, Lachnospira, and Prevotella had potential positive correlation with positive mood, while genera Faecalibacterium, Bifidobacterium, Bacteroides, Parabacteroides, and Anaerostipes were correlated with negative mood.

Gut microbes in correlation with mood: case study in a closed experimental human life support system. Neurogastroenterol Motil. 2016 Mar 29.

Microbiota and Mental Health

• PTSD, Anxiety, Depression,

• Cognition, Learning • Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key? Can J Psychiatry. 2016 Apr;61(4):204-213.

Epub 2016 Feb 24.• Probiotics as an adjuvant therapy in major depressive disorder. Curr Neuropharmacol. 2016 May 26.• Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children. Nutr Rev.

2016 May 3. pii: nuw008. • Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.• Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior. PLoS One.

2016 Jan 8;11(1):e0146406• Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience. 2015 Aug

6;300:128-40. doi: 10.1016/j.neuroscience.2015.05.016. Epub 2015 May 14.• From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016

Jun;21(6):738-48. doi: 10.1038/mp.2016.50. • Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients.

2016 Jan 20;8(1). pii: E56• Gut microbes in correlation with mood: case study in a closed experimental human life support system.

Neurogastroenterol Motil. 2016 Mar 29.

Obesity and Microbiome

• Differing gut microbiome – between obese, overweight and healthy adults

• Adding fiber to the diet improves insulin sensitivity, reduces metabolic syndrome, reduces inflammation and obesity in animal models of obesity, insulin resistance

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. Cell Host Microbe. 2017 Dec 12. pii: S1931-3128(17)30497-3Dysbiosis Signatures of Gut Microbiota Along the Sequence from Healthy, Young Patients to Those with Overweight and Obesity. Obesity (Silver Spring). 2017 Dec 27

Microbiota and Heart Disease

• Trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development.

• TMAO linked to gut microbes. (meat)

• HDL linked to gut microbes

The gut microbiota - an emerging risk factor for cardiovascular and cerebrovascular disease. Eur J Immunol. 2017 Dec 12Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio. 2015 Mar 17;6(2):e02481Microbiota and HDL metabolism. Curr Opin Lipidol. 2017 Nov 11.

Inverse Relationship Between Hygiene and AD

…hygiene is positively

associated with AD risk.

Countries with greater

degree of sanitation and

lower degree of pathogen

prevalence have higher

age-adjusted AD DALY

rates.”

Fox M, Knapp LA, Andrews PW, Fincher CL. Hygiene and the world distribution of

Alzheimer’s disease: Epidemiological evidence for a relationship between microbial

environment and age-adjusted disease burden. Evolution, Medicine, and Public Health.

2013;2013(1):173-186. doi:10.1093/emph/eot015.

Fox M, Knapp LA, Andrews PW, Fincher CL. Hygiene and the world distribution of

Alzheimer’s disease: Epidemiological evidence for a relationship between microbial

environment and age-adjusted disease burden. Evolution, Medicine, and Public Health.

2013;2013(1):173-186. doi:10.1093/emph/eot015.

Human gut microbiota: the links with dementia development

Cytokine release Gut hormonesVagal nerve. NP: Neuropeptide; NT: Neurotransmitter; 5-HT: 5-hydroxytryptamine; DC: Dendritic cell; EEC: Enteroendocrine cell; Aβ: amyloid beta protein; AD: Alzheimer’s disease

Alkasir R, Li J, Li X, Jin M, Zhu B. Human gut microbiota: the links with dementia development. Protein & Cell. 2017;8(2):90-102. doi:10.1007/s13238-016-0338-6.

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1, Laman JD2, 't Hart BA2,3.Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol. 2017; 8: 1081.

Vegetables and Microbiota in RRMS • N=20 high vegetable/low protein vs. SAD

• 1 year

• Change in microbiota

• Change in inflammatory cytokines, microbiota

• Relapses 9/10 in Western diet vs. 3/10 in high vegetable diet

Immunological and Clinical Effect of Diet Modulation of the Gut Microbiome in Multiple Sclerosis Patients: A Pilot Study. Front Immunol. 2017 Oct 25;8:1391.

• Microbiome begins with Mom

"Breastfeeding infant" by Ken Hammond ([1]) - USDA. Licensed under Public Domain via Commons -https://commons.wikimedia.org/wiki/File:Breastfeeding_infant.jpg#/media/File:Breastfeeding_infant.jpg

Microbiome Beginnings

• Vaginal delivery

• Face towards the rectum at delivery – Bifidobacter colonize gut

• C-section babies • Higher rates of obesity, asthma, diabetes, mental

health problems, autoimmunity

– Staph and Strep colonize the gut

– Vaginal secretions swab face and body

Signs a of Trouble

• Colic

• Constipation

• Diarrhea

• Frequent infections / antibiotics

• Rashes

• Neurobehavioral problems

• Autoimmune problems

"BristolStoolChart" by Cabot Health, Bristol Stool Chart - http://cdn.intechopen.com/pdfs-wm/46082.pdf. Licensed under CC BY-SA 3.0 via Commons -https://commons.wikimedia.org/wiki/File:BristolStoolChart.png#/media/File:BristolStoolChart.png

"Human Feces" by User Cacetudo on en.wikipedia - Own work. Licensed under CC BY-SA 2.5 via Commons -https://commons.wikimedia.org/wiki/File:Human_Feces.jpg#/media/File:Human_Feces.jpg

Stop processed foods, gluten, dairy, eggs

More Vegetables

"Kombucha Mature" by Mgarten at the English language Wikipedia. Licensed under CC BY-SA 3.0 via Commons

Family Time

Home Economics Family

Adult skills Social skills BehaviorsAcademics

Economic security Health outcomes

Nutrition

• Therapeutic Lifestyle Classes

• Group Classes

• Introduction to concepts

• Intake half day

• 2 Hr MD – Timeline and Matrix

• 2 HR RD Healthy Kitchen

© Dr. Terry Wahls LLC, All Rights Reserved. 51

• Support groups every other month

• Skills classes every month

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• Chronic pain (55%)

• Metabolic Issues (25%)

• Autoimmune (15%)

• TBI

• Fibromyalgia

• Mood disorders

© Dr. Terry Wahls LLC, All Rights Reserved. 53

Reasons for Referral

Outcomes Biometric

• Comparing those with 1 visit to 3+ visits

• BMI ↓

• Hgba1c ↓

• Trig/ Hdl ratio ↓

• Vitamin D ↑

• Homocysteine ↓

How many cups of vegetables did you eat in last 24 hours?

In Person Events

Wahls Protocol® Seminar

Health Practitioner Workshop

Health Professional Certification

• Instagram @drterrywahls

• Facebook @Terry Wahls MD

• Twitter @TerryWahls

• info@wahlsinstitute.com

• www.terrywahls.com

• Copies of Wahls MS papers and links to video of gait changes www.terrywahls.com/papers

• Contact MSDietStudy@healthcare.uiowa.edu