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Early Immune Education

Life’s lessons from our microbiota

In 2012, I was given a challenge for a special issue of the journal, Entropy: to identify the single most useful sign that distinguishes a life of health from one filled with disease. After an unsatisfactory attempt to develop a cohesive concept, I slept on it, only to awaken from a dream with the fully-formed concept of superorganism self-completion. That is, we need to complete ourselves as a majority microbial, human superorganism: a symbiotic organism. That is our complete, natural, healthy state.1 This is the focus of a new documentary film “Microbirth” that is due to be released in September.

During pregnancy, birth, and early infant development, anything that interferes with the formation of “The Completed Self” (e.g., exposure to toxic chemicals and drugs, antibiotic administration, Cesarean delivery, formula feeding, stress) can result in microbial dysbiosis, immune dysfunction, and increased health risks for the child. That early-life status of our microbial majority affects later-life health should not be a complete surprise. The groundwork for this idea was laid via two major tenets connecting developmental status with later-life disease: The Barker Hypothesis and The Hygiene Hypothesis. As described by microbiology professor Graham Rook at University College London, we are designed to live in nature’s biodiverse ecosystem encountering our old microbial friends as part of our early immune education.2

The microbiota in our skin and various mucosal tissues such as the gut, occupy the portals through which we communicate seamlessly with our external environment. Most importantly, once seeded, our microbiota co-matures with our immune system, enabling the immune system to better recognize actual environmental threats to the organism. In the absence of this co-maturation, improper, misdirected, and unresolving immune responses and inflammation result. Dysbiosis of the microbiota is likely to be a key factor in the current epidemic of non-communicable diseases (NCDs) and conditions.3 When the microbes that are tailored to be a part of us are missing, we literally tear ourselves apart via tissue-directed immune dysfunction including autoimmune and allergic reactions, and misregulated inflammation.

The Seeds of Good Health
Recent evidence from the Kasper and Blumberg groups at Harvard suggests that critical windows of development exist shortly after birth in which a diverse and appropriate microbiota needs to be in place to prevent later life immune dysfunction and inflammatory disease.4 That means it is important to get the microbial seeding process right surrounding birth. While later treatment to correct microbiome dysbiosis may help restore gut microbe balance, the benefits could be limited since key immune maturational windows may have already been missed leaving disease-promoting immune dysregulation in place.

Microbe metabolism appears to be important in this process in the developmental processes leading to health vs. disease with lipid and fatty acid bacterial metabolites providing at least one route for functional shifts in immune cells and as well a specific tissues.5.6.7 Therefore, fully understanding the metabolonomics of how our microbiota interact with the environmental, metabolize nutrients, chemicals and drugs and help to shape our organ composition and function is an important step toward effective personalized medicine.

Self-completion is not only about risk of childhood and adult disease. Our microbiome appears to affect our personality profile including behavior 8, metabolically-driven dietary preferences9 and familial and societal interactions.9 With gut microbiota metabolically molding our persona, our majority microbes really do help to define who were are.

Given the pivotal role that our microbiota plays in the ongoing NCD epidemic, a refocus on the newly-defined, whole human is needed. We can calibrate our progress by asking a few simple questions. Do we feed ourselves to support a balanced and diversified microbiota? Does our regulated drug and chemical safety assessment process (e.g., in vivo and in vitro toxicity testing) account for risk to the microbiota? Do we medically manage pregnancy and infant development to ensure diversified microbial seeding of the newborn and nutrient support of the microbiota in the infant? If not, then a refocus is warranted. We need to birth, nourish, and medically manage humans as intended: a majority-microbial, healthy, superorganism. Such an approach could help to reduce the prevalence of immune and microbial dysregulation as well as the NCDs. We are indeed more than meets the eye.


Additional Information:
The feature-length documentary, “Microbirth” due to premiere this fall suggests that what happens during childbirth has implications for the future health of our children and potentially for the whole of mankind. Watch it on here.


References

  1. Dietert RR, Dietert JM. The completed self: an immunological view of the human-microbiome superorganism and risk of chronic diseases. Entropy. 2012; 14(11), 2036-2065.
  2. Rook GA. Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18360-7.
  3. Martinez FD. The human microbiome. Early life determinant of health outcomes. Ann Am Thorac Soc. 2014 Jan;11 Suppl 1:S7-12.
  4. An D, Oh SF, Olszak T, Neves JF, Avci FY, Erturk-Hasdemir D, Lu X, Zeissig S, Blumberg RS, Kasper DL. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell. 2014 Jan 16;156(1-2):123-33.
  5. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013 Dec 19;504(7480):446-50.
  6. Macfabe D. Autism: metabolism, mitochondria, and the microbiome. Glob Adv Health Med. 2013 Nov;2(6):52-66.
  7. Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TM. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans.  Int J Obes (Lond). 2014 Mar 19. doi: 10.1038/ijo.2014.46.
  8. Farmer AD, Randall HA, Aziz Q. It's a Gut Feeling - how the gut microbiota affects the state of mind. J Physiol. 2014 Mar 24. doi:10.1113/jphysiol.2013.270389.
  9. Martin FP, Montoliu I, Nagy K, Moco S, Collino S, Guy P, Redeuil K, Scherer M, Rezzi S, Kochhar S. Specific dietary preferences are linked to differing gut microbial metabolic activity in response to dark chocolate intake. J Proteome Res. 2012 Dec 7;11(12):6252-63.
  10. Crumeyrolle-Arias M, Jaglin M, Bruneau A, Vancassel S, Cardona A, Daugé V, Naudon L, Rabot S. Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.  Psychoneuroendocrinology. 2014 Apr;42:207-17.

Dr. Rodney Dietert, Ph.D. is Professor of Immunotoxicology in the Department of Microbiology and Immunology at Cornell University, Ithaca, NY, and has been on the Cornell faculty for 37 years. He has more than 300 publications with the majority focused on early-life environmental risks factors for the developing immune system and prevention of non-communicable diseases. He is currently editor of Springer’s toxicology book series: Molecular and Integrative Toxicology.

 

Comments
marodon
Great text! Is micro biome the missing link between science and holistic medicine? we should treat people rather than disease? And should we stop antibiotics altogether?
5/23/2014 8:10:39 AM

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