artwork by Scott Draves (www.electricsheep.org)

Rodney Dietert, Professor

Cornell University

rrd1@cornell.edu

How to Train Your Superorganism

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

• 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

Outline

1. How I found my Superorganism

2. What I learned from my Superorganism

3. How I trained my Superorganism (and you can too)

How I Found My Superorganism

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]

My Answer(upon waking from a dream)

Self completion of the

human-microbial superorganism

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

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

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

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

set.

What I Learned From My Superorganism

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% microbialby cell number

Second ~ 10 million genes

Superorganism

Mammalian

MicrobialEukaryotes

Archaea – also in your gut

Earlier Microbial PartnersLynn 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.

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).

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 doghttp://www.dailymail.co.uk/health/article-2247688/Meet-Cliff-remarkable-super-sniffing-dog-detects-hospital-superbugs.html

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

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.

Effective Microbiome-Mediated Immune Maturation

Ineffective Microbiome-Mediated Immune Maturation

Managing the Human Ecosystemfor Effective Immune Maturation and Tolerance

Brain – Who’s Running the Show?

Foodpreferences 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;

Misregulated Inflammation

is

A feature of gut microbial dysbiosis

A tie that binds non-communicable

diseases and conditions (NCDs)

together

From: Dietert, DeWitt, Germolec and Zelikoff , Environ. Health Perspect. 118:1091-9, 2010

Non-Communicable Diseases Cluster Together

Diabetes, Obesity,Colitis, Asthma,Celiac disease

Diabetes, ObesityColitis,Asthma,Celiac disease

microbiomeadjustmentas part ofadultdisease management

microbiomeadjustment for pregnancy and to optimizemicrobiome seeding

Birth:Vaginalvs.Cesarean

healthy microbiome seeding plan

feeding the microbiotafor optimizedimmune and microbialco-maturation

Risk offuturegenerationsforvariousimmunedysfunction-promoted NCDs

Perinatal Period

Is it safe?The New “Organism” for Safety

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)

The Microbiome Filters Virtually All Exposuresand 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

How I Trained My Superorganism(and you can too)

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 itmedical advice.

Alexander Fleming’s Microbial Art

Notice the bottle feeding – probably not with breast milk

Image via:The Alexander Fleming Laboratory Museumand Smithsonian exhibition

Da Vinci in Microbes

http://www.wired.com/2012/09/bacteriogoraphy/?pid=3733

Zachary Copfer,microbiologist and photographer.He microbially“grows”the photographic images.

Microbial Tree of Life

From: http://www.microbialart.com/

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

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.

Links to some open-access papers

(you can download the papers for free)

http://www.mdpi.com/1099-4300/14/11/2036

Original Completed Self paper (2012):

The microbiome and sustainable healthcare (2015)

http://www.mdpi.com/2227-9032/3/1/100

http://www.hindawi.com/journals/amed/2014/867805/

Programming of the immune system for non-communicable diseases (2014)

http://microbirth.com/

Microbirth movie site: Note for all Cornell people, the movie is freely-available for streaming from Kanopy via the Cornell Library site.

http://ehp.niehs.nih.gov/wp-content/uploads/118/8/ehp.1001971.pdf

Clusters of non-communicable diseases (free PDF)

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

Thank You!

Discussion

…….and YoghurtThanks to Ithaca Water Buffalo

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