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“You” Are Not You, But “We”: How The Microbiome May Change Everything.

Posted May 27 2013 10:01pm

Posted on | May 24, 2013 |

In 2003, I was moderating a Q&A session with Craig Venter, the American biologist and entrepreneur of DNA mapping fame. On behalf of the audience, I asked him what percentage of the knowledge required to optimally care for human beings did we currently possess. His unhesitant response?  “Less than one percent.” Over the years I’ve wondered a bit whether that was an exaggeration. But this week I became a true believer.

My full conversion came at the hands of Michael Pollan’s New York Times Magazine article titled “Some of My Best Friends Are Bacteria”.(1) I’ve been a fan of Pollan – the citizen scientist, food expert and brilliant investigative environmental and ecological journalist – for a number of years. But now Pollan has decided to not leave food on the table, but instead follow it directly into the human gut. And what he reveals, on behalf of leading edge gastrointestinal researchers is nothing short of revolutionary and mind-altering for medical science.

What’s the big picture? Well to start with, you may think of “you” as you, but “you” are largely “them”. On the average, you carry about 2 pounds of microbes, largely in your intestinal tract. That includes some 100 trillion organisms, with hundreds of varieties, including non-invasive freeloaders, mutually beneficial symbiotics, and occasional harmful pathogens. Only 10% of the genomic material in your body is your own. The other 90% is possessed by these organisms, now termed your “second genome”, or your “microbiota” or “microbiome”.(1, 2)

In 2010, professors at the Center for Ecology and Evolutionary Biology at the University of Oregon published a landmark review article  titled, “From Structure to Function: The Ecology of Host-Associated Microbial Communities”. The authors created quite a stir when they said we humans needed to think of ourselves not as individuals but as communities, or in their words, “a collective property of the human-associated microbiota”. (3)

Going one step further, and reflecting on the fact that the average human gastrointestinal tract manages the passage of 50 tons of food in a lifetime, the authors suggested that much of that food goes to feeding the microbiome, a teeming collective life form essential to our survival, and integrated into all of our major homeostatic mechanisms. Further they suggested that feeding the microbiome the wrong types of food led to adjustments in the varied colonies of organisms, which in turn resulted in altered gut permeability and inflammatory reactions, and possibly common pathways to chronic diseases including diabetes, auto-immune diseases, cardiovascular disease, and cancer.(1,3)

It seems that intestinal epithelial cells are an internal type of skin that plays by very different rules. Where most cells receive nourishment through molecules distributed by our extensive vascular system, our colonic epithelial cells feed on short-chain fatty acids derived from intestinal bacteria driven fermentation of plant fiber in the large intestine.(2)

So we’re harboring a hidden world down there, a world that must be fed and treated properly if we are to thrive. But the story does not end there. It seems that evolutionary wise, we’ve outsourced a wide range of functions to this “second genome”, experts believe, because they are capable of managing normal and abnormal physiology better and quicker than our primary genome.(1,2,3)

Understanding the complexities of this huge and hidden wilderness is in its infancy. But what scientists have uncovered in just the last year or two, through the use of new gene sequencing technology to map the microbiome, is pretty startling including:

1. Our microbiome manufactures a variety of substances including the neurotransmitter  serotonin, enzymes, vitamins, amino acid and short-chain fatty acids, and signaling molecules that help modulate our immune and the metabolic systems.(2,3)

2. While involving itself in fundamental physiologic feedback cycles, the microbiome is also managing the speed, motility and efficiency of the movement of food through the human gut, and at the same time keeping a close eye on its own needs for food. Each organism has somewhat different needs. So the food we chose helps tip our microbiota in the direction of those microbes who like the diet we’ve selected for them.(1,2,3)

3. It turns out that scientists have been doggedly pursuing fecal samples in young and old here, there, and everywhere. Initially, newborns guts are sterile. Most of the bacteria are inherited from the mother when babies pass through the microbial rich birth canal. Babies born by C-section, lack this natural insemination. Their microbial guts early on resemble mostly the microbe colonies of mother and father’s skin. Babies who are breast fed have a different microbiome than those who are not. By age three, children have a nearly adult microbiome.(1,2)

4. Individuals in less developed nations have a more diverse micobiome which may in part be the reason they exhibit less inflammatory and chronic diseases than those in the developed world. At the same time, this diversity results in higher rates of morbidity and mortality from infectious pathogens.(2,3)

5. Our overuse of antibiotics clearly represents an assault on our microbiomes, and is life altering for the many microbial species we support as part of the “second genome’. But in addition, it likely has significant implications for basic physiologic mechanisms. For example, livestock producers have for many years used feed laced with low dose antibiotics because it is known to speed up growth of animals. Where it used to take 6 years to bring a cow to market, it now takes 18 months.(4,5) Might childhood obesity be similarly favored considering that the average American child ingests 10 to 20 courses of antibiotics before age 18?(1)

6. Where our personal genome is relatively rigid, fixed, and slow to adapt, our “second genome” is far more malleable and open to manipulation.(2,3) For example, individuals critically ill with Clostridia difficile have been successfully treated with fecal transplants donated from normal individuals.(6) If the microbiome can be positively impacted by treatment from below, could the same be true from above? Scientists involved in the field agree the answer is yes. Expect the rapid emergence of “therapeutic foods”.(1) But be aware of a high rate of fraud until regulations catch up. For example, one study of 14 probiotic products revealed that only one of them contained the microbes promised on the label.(7)

7. The American highly processed, additive rich, fast food diet favors upper GI quick feeding at the expense of lower GI slow fermentation. The resultant microbiome may be leading to gut epithelial permeability, inflammatory responses and numerous chronic disease entities.(1,2,3)

Clearly this is just the beginning. But it does point the way toward some actions now, according to the experts. These include:

1. A more cautious approach to the use of antibiotics.

2. A more relaxed sanitary regimen. Super sterile environments result in less microbiome diversity. Greater diversity overall is beneficial.

3. Elimination or serious reduction in processed food that discourages fermentation in the colon. To feed bugs well think Al dente pasta, steel-cut oats, raw or lightly cooked vegetables, home preparation, slow food and slow digestion.  As Pollan says,  “This is at once a very old and a very new way of thinking about food: it suggests that all calories are not created equal and that the structure of a food and how it is prepared may matter as much as its nutrient composition… With our diet of swiftly absorbed sugars and fats, we’re eating for one and depriving the trillion of the food they like best: complex carbohydrates and fermentable plant fibers.”(1)

Stay Tuned!

For Health Commentary, I‘m Mike Magee

References.

1. Pollan M. “Some of my best friends are bacteria”. NYT Magazine. May 19,2013. http://www.nytimes.com/2013/05/19/magazine/say-hello-to-the-100-trillion-bacteria-that-make-up-your-microbiome.html?pagewanted=all&_r=0

2. Lozupone CA et al. Diversity, stability and resilience of the human gut microbiota. Nature.489:7415, Sept. 13, 2012. http://www.nature.com/nature/journal/v489/n7415/full/nature11550.html

3. Robinson CJ, et al. From Structure to Function: The Ecology of Host-Associated Microbial Communities. Microbiology and Molecular Biology Reviews. 74(3):453-476. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937523/

4. Gaskins HR et al. Antibioptics as growth promotants: Mode of action. Animal Biotechnology. 13:1,2002. http://www.tandfonline.com/doi/abs/10.1081/ABIO-120005768#.UZ-TEjl7SHU

5. Pollan M. The Omnivore’s Dilemma. The Penquin Press. 2006. http://www.amazon.com/The-Omnivores-Dilemma-Natural-History/dp/1594132054

6. Kelly CP, LaMont JT. Clostridia difficil – More Difficult Than Ever. NEJM. 2008;359:1932-40. http://elearning6.ttuhsc.edu/som/internalmedicine/general/education/must_reads/documents/clostridium_difficile_nejm_oct2008.pdf

7. Marcobal A, Underwood MA, Mills DA. Rapid determination of the bacterial composition of commercial probiotic products by terminal restriction fragment length polymorphism analysis. J. Pediatric Gastrointestinal Nutrition. May, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18493222

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