How to Train Your Superorganism

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artwork by Scott Draves ( Rodney Dietert, Professor Cornell University [email protected] How to Train Your Superorganism

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Question? Allergies (food/ asthma/rhinitis/dermatitis) Cancer Obesity Diabetes Cardiovascular disease Arthritis Autism spectrum ADD/ADHD Celiac disease IBD (Crohn’s, UC) Lupus Autoimmune thyroiditis Depression Osteoporosis Frailty Dementia Alzheimer’s disease Parkinson’s disease Hypertension Sleep disorders PCOS COPD Chronic kidney disease Psoriasis Multiple sclerosis

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Already the Number #1 Cause of Mortality Worldwide (63%)* Dramatically Impacts Both Productivity and Quality of Life Estimated to Cost 48% of Global GDPs by 2030* Most Chronic Diseases are Increasing in Prevalence 45.3% of all US adults age 65 and above have two or more chronic diseases: a 20% increase from the previous decade.* *Joint 2011 report: Harvard School of Public Health and World Economic Forum and NCHS Data Brief Number 100, July 2012 Noncommunicable Diseases and Conditions (NCDs) are the Greatest Threat to Sustainable Healthcare

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Outline How I found my Superorganism 2. What I learned from my Superorganism 3. How I trained my Superorganism (and you can too)

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How I Found My Superorganism

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Scientific Challenge If you could pick ONE sign that best distinguishes a lifetime of health from one filled with disease ……what would that be???? [Challenge was issued for an invited paper for a special issue of the physics journal ENTROPY]

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My Answer (upon waking from a dream) Self completion of the human-microbial superorganism

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The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases Entropy 2012, 14 (11), 2036-2065 R Dietert, J Dietert

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Self-Completion - The Completed Self Host-specific, Family-sourced microbiota Self Completion See: Dietert and Dietert, Entropy 14(11), 2036-2065, 2012 and Dietert, Birth Defects Research Part B. 101(4): 333-340, 2014

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2014 documentary film Wellcome Trust screening – Jan. 30, 2015

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Note: the brief Microbirth film clips were excluded from this slide set.

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What I Learned From My Superorganism

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The Complete Human: Three Domains of Life Eukaryota Archaea Bacteria Majority- Microbial Humans (based on cell and gene numbers) Domains of Life Genomes First ~ 25,000 genes Approximately 90% microbial by cell number Second ~ 10 million genes Superorganism Mammalian Microbial Eukaryotes

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Archaea – also in your gut

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Earlier Microbial Partners Lynn Marguluis, famed biologist (former spouse of Carl Sagan), published her endosymbiosis theory in 1967concerning the bacterial origins of both mitochondria and chloroplasts. Crisp et al. Genome Biology 2015, 16:50 New examples of horizontally transferred genes were recently identified in humans. Apparently, our second genome can become part of our first genome.

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Our Microbiome Produces a “Fingerprint” of Volatile Organic Compounds (VOCs) Arasaradnam et al. PLoS One. 2014 Oct 16;9(10):e107312. Volatile organic compounds (VOCs) in urine can be used to differentiate celiac disease from irritable bowel syndrome based on distinctive microbiome-produced metabolites. Bezerra de Araujo Filho et al. Archaea. 2014 Oct 13;2014:576249. Children living near a sanitary landfill had elevated breath methane correlated with elevated methane producing Archaea in the gut microbiome (unrelated to socio economic status).

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Microbial Dysbiosis and Impending C. Difficile Outbreaks See: Bomers et al. A detection dog to identify patients with Clostridium difficile infection during a hospital outbreak. J Infect. 2014 Nov;69(5):456-61. Cliff, the original C. Difficile detection dog

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Who are you really? and…. How (healthy) are you?

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Microbiota are seen as an “Integral Organ” If they are missing, it analogous to a form of birth defect. Ramifications of Self Incompleteness e.g., Clarke et el., Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014 Aug;28(8):1221-38. Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med. 2015 Jan 14;66:343-59. Evans et al. The gut microbiome: the role of a virtual organ in the endocrinology of the host. J Endocrinol. 2013 Aug 28;218(3):R37-47.

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Effective Microbiome-Mediated Immune Maturation Ineffective Microbiome-Mediated Immune Maturation Managing the Human Ecosystem for Effective Immune Maturation and Tolerance

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Brain – Who’s Running the Show? Food preferences and cravings Neurobehavior Kin recognition Mating behavior See: Lize et al., Trends Ecol Evol. 2013 Jun;28(6):325-6; Alcock et al. Bioessays 36(10): 940-949 2014;

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Misregulated Inflammation is A feature of gut microbial dysbiosis A tie that binds non-communicable diseases and conditions (NCDs) together

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From: Dietert, DeWitt, Germolec and Zelikoff , Environ. Health Perspect. 118:1091-9, 2010 Non-Communicable Diseases Cluster Together

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Diabetes, Obesity, Colitis, Asthma, Celiac disease Diabetes, Obesity Colitis, Asthma, Celiac disease microbiome adjustment as part of adult disease management microbiome adjustment for pregnancy and to optimize microbiome seeding Birth: Vaginal vs. Cesarean healthy microbiome seeding plan feeding the microbiota for optimized immune and microbial co-maturation Risk of future generations for various immune dysfunction- promoted NCDs Perinatal Period

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Is it safe? The New “Organism” for Safety

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Environmental chemicals and drugs reported to affect the gut microbiome (Note added: In contrast with antibiotics, Vitamin D is on the list because it affects, but does not necessarily “harm,” the microbiome. Many people are, in fact, deficient in Vitamin D. In the Ooi et al. paper listed below, it shifts the microbiome to increase protection AGAINST colitis) Heavy metals (e.g., cadmium, lead, arsenic) Other metals (iron, selenium, zinc) PCBs (Choi et al., EHP 2013) Particulate matter (PM10) (Kish et al. PloS One 2013) Chlopyrifos (Joly et al, ESPRI, 2013) High fat diet (Myles et al. Plos One 2014) Valproate (de Theije et al. Brain Behav Immun 2013) Antibiotics (Ng et al., Nature 2013) Vitamin D (Ooi et al., J.Nutr 2013)

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The Microbiome Filters Virtually All Exposures and Directly Participates in Epigenetic Alterations Proposed New Environmental Health Assessment Model Adapted from: Dietert and Silbergeld, Toxicol. Sci. in press, April 2015 print issue Microbiome

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How I Trained My Superorganism (and you can too)

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My Personal Superorganism Later-Life Training Problem: 30 years of multiple rounds of antibiotics. each year. Solution: Adjusted my microbiome, adjusted what I fed it. Best year for my health in at least 30 years. Qualifications: I am not a MD. This is my personal story and it is not intended to be nor is it medical advice.

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Alexander Fleming’s Microbial Art Notice the bottle feeding – probably not with breast milk Image via: The Alexander Fleming Laboratory Museum and Smithsonian exhibition

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Da Vinci in Microbes Zachary Copfer, microbiologist and photographer. He microbially “grows” the photographic images.

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Microbial Tree of Life From: Credits to: Dr. T. Ryan Gregory (Canada), Dr. Simon Park (United Kingdom), and Dr. Niall Hamilton (New Zealand).

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Three Take-Home Points Failure to self-complete in the newborn may be the single greatest health risk across a lifetime. We need microbiome seeding on every birth plan and active management of our “second genome” (i.e., seed, feed, protect). The immune system and the microbiome need to co-mature in a narrow window of development or persistent immune dysfunction and elevated risk of NCDs are likely. Safety needs to be based on the whole human. It is the superorganism that needs protection.

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Links to some open-access papers (you can download the papers for free) Original Completed Self paper (2012): The microbiome and sustainable healthcare (2015) Programming of the immune system for non-communicable diseases (2014) Microbirth movie site: Note for all Cornell people, the movie is freely-available for streaming from Kanopy via the Cornell Library site. Clusters of non-communicable diseases (free PDF)

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Acknowledgements Dr. Ellen Silbergeld, Johns Hopkins School of Public Health co-author and co-developer of the new environmental health model Janice Dietert, Performance Plus Consulting, co-author and editor

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Thank You! Discussion …….and Yoghurt Thanks to Ithaca Water Buffalo

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Ithaca Water Buffalo Ithaca Water Buffalo maintains a herd of 100 female animals. Water Buffalo produce about 2 gallons of milk a day. Milk is heated and pasteurized (170? F for 30 min) Milk is cooled to 100?F Yogurt Culture is added Cultured Milk is placed in the cup Milk is incubated ay 100?F for ~ 12 h “Probiotic” Bacteria ferment the milk sugar (lactose) into acid (lactic acid) Yogurt is blast chilled to 36? F to “set” the solid Yogurt is boxed and shipped to the store