Gut Microbiome

Anthropocentric Error

What causes disease? At the turn of the 21st century, scientists proposed that the answers lay hidden in the genetic code of humans. They believed that genetic mutations--errors in DNA sequences--were the source of many diseases. The scientific community believed that finding these errors would allow for their correction, thereby curing diseases. 

So, the Human Genome Project, a plan to sequence the entirety of a human's DNA, was born. The strategy would be to compare the DNA of a sick individual with the DNA of a healthy control. Differences in DNA between the two individuals would reveal the underlying genetic error producing the disease. The next step would be to repair these errors, and voila, cure! Easy enough, right?

Wrong. First, DNA manipulation is extremely difficult. Remember, you have 10 trillion cells derived from your DNA; that's a lot of errors to correct. And, even if this were currently feasible, these elusive DNA errors--driving obesity, type II diabetes, high blood pressure, etc.--largely haven't been found.

Do you know why?

The problem isn't your genes.

The problem is your behavior.

Your behavior--what you eat, how much you move, what activities you engage in--shapes your bacterial fingerprint, the unique populations of bacteria inhabiting your body. Collectively, the bacteria in your body contain 100 times the number of genes contained in your own genome. So, the scientists expanded the scope of their genetic sequencing project to create the Human Microbiome Project, a plan to sequence the DNA of the 100 trillion microorganisms sharing your body. 

An obsession with the human genome overlooked a very important fact: animals have co-evolved with bacteria, viruses and fungi for hundreds of millions of years. These microbes are just as much a part of you as you are. Scientists are at the precipice of understanding the interface of humans and their microbiota, and how these relationships affect human health.

It's time to dismiss this naive anthropocentrism. The key to longevity isn't repairing errors in your DNA.

The key to longevity is optimizing the symbiotic potential of your microbiome.

It’s now undeniable that our intestinal organisms participate in a wide variety of physiologic actions, including immune system functioning, detoxification, inflammation, neurotransmitter and vitamin production, nutrient absorption, signaling being hungry or full, and utilizing carbohydrates and fat. All of these processes factor mightily into whether or not we experience allergies, asthma, ADHD, cancer, diabetes, or dementia. The microbiome affects our mood, libido, metabolism, immunity, and even our perception of the world and the clarity of our thoughts. It helps determine whether we are fat or thin, energetic or lethargic. Put simply, everything about our health―how we feel both emotionally and physically―hinges on the state of our microbiome. Is it healthy and dominated by so-called friendly, beneficial bacteria? Or is it sick and overrun by bad, unfriendly bacteria?
— David Perlmutter, MD (Brain Maker, pg. 9)
 

Colonization

How did the bacteria take up residence in your gut in the first place?

What determines why one species of a bacteria is present rather than another?

What can you do to ensure that your next child has a healthy, diverse array of intestinal bacteria?

The period of time extending from fertilization of an egg to the first years of life is absolutely critical in determining the microbial inhabitants of the gut. The three most important factors include: mode of delivery, source of nutrition and exposure to antibiotics (Mueller et al.).

Vaginal delivery or C-section

Passage through the vaginal canal is the most important event in exposing the newborn to healthy bacteria. It's like a

#VaginalBaptism

A mother's vagina houses the bacteria designed to be the first inhabitants of a newborn's digestive tract. The vagina contains bountiful Lactobacillus, a popular probiotic and a bacterial strain capable of digesting lactose, the carbohydrate contained in mother's breast milk.

Compare this to the digestive tracts of children born by C-section, which are colonized with bacteria on mother's skin: Staphylococcus, rather than Lactobacillus. Dr. Perlmutter asserts that disrupting this critical colonization by performing C-section increases the risk of a wide spectrum of disease: 

  • Allergies: 5x increase
  • ADHD: 3x increase
  • Autism: 2x increase
  • Celiac disease: 80% increase
  • Type 1 diabetes: 70% increase
  • Obesity as an adult: 50% increase

Of course, if the health of the mother or fetus is at risk, C-section should be performed without hesitation. However, pursuing C-section out of preference is doing a disservice to the future health of the child.

Breast milk or Formula

Following birth, diet plays a pivotal role in further development of the gut microbiome. Will the infant be fed breast milk or formula?

Aside from providing essential nutrition, breast milk contains probiotics (bacterial species e.g. Bifidobacteria) and prebiotics (nutrients which promote growth of certain bacterial species). Breast milk also contains antibodies which bolster the infant's nascent immune system.

Infants are designed to consume mother's milk, not a powdered substitute concocted in a science lab. In comparison with formula-fed infants, breast-fed infants possess a higher concentration of Bifidobacteria, a bacteria well known for healthful benefits and also a popular probiotic. 

Antibiotics or No antibiotics

Antibiotics kill indiscriminately. Antibiotics taken by the mother--whether during pregnancy, proceeding C-section, or while breast feeding--can damage the microbiome of the child. Many antibiotics cross the placenta and are secreted in breast milk. 

Antibiotics given to the infant--most commonly for ear infections or upper respiratory tract infections--early on in life can adversely affect the microbiota. Antibiotics should be used with extreme caution and only when medically necessary.

 

Digestive Tract

 From missinghumanmanual.com

From missinghumanmanual.com

The human digestive tract extends from the oral cavity to the anus, including the mouth, esophagus, stomach, small intestine and colon.

The colon houses the largest number of bacteria and the stomach houses the least number of bacteria given the inhospitable acidic environment.

The relationship between humans and their gut microbes should be one of symbiosis, a relationship of mutual benefit.

Humans provide food and lodging for the bacteria, who perform essential roles for their human host:

  • Digestion & Absorption
    • Processing fiber indigestible by humans
  • Synthesis
    • Production of vitamins: K, B1 [Thiamine], B9 [Folic acid], B12 [Cyanocobalamin]
    • Production of neurotransmitters
    • Production of short chain fatty acids [SCFA], which are "an important source of energy from non-digestible carbohydrates. SCFAs are immunomodulatory, inhibit common pathogens, and are hypothesized to possess tumor-suppressive properties" (Lloyd-Price et al).
  • Immune function
    • Educating the immune system about which bacteria are symbiotic and which are pathogenic; the gut is the largest immune system organ!
    • Creating a biofilm and blocking entry of invading microbes
    • Preventing autoimmune disease
 

Gut Dysbiosis

Generally speaking, a healthy microbiome is characterized by a diversity of microorganisms.

Intestinal dysbiosis is characterized by a lack of diversity among bacterial species in the gut. Gut dysbiosis can present with a range of symptoms including: flatulence, bloating, diarrhea, constipation, obesity and abdominal tenderness.

Disease states believed to be associated with dysbiosis of the gut include:

  • Irritable Bowel Syndrome
  • Inflammatory Bowel Disease [Crohn's Disease & Ulcerative Colitis]
  • Type I diabetes
  • Prediabetes and Type II diabetes
  • Obesity
  • Kidney stones

Although the clinical manifestations of these diseases vary widely, they share one underlying commonality: a lack of diversity among the gut microbiome (Heiman & Greenway).

Why does gut dysbiosis occur? Simply put, a dramatic shift in agricultural production and parallel shift in dietary consumption.

Three quarters of the global food supply is derived from a mere 12 plant and five animal species (Heiman & Greenway). Lack of agricultural diversity leads to lack of intestinal microbial diversity. Furthermore, "Agricultural practices of using antibiotics as growth promoters for poultry, swine and cattle further narrow the GI microbiome" (Heiman & Greenway). A similar effect could be proposed regarding the effect of plant pesticides on the gut microbiome.

The "disappearing microbiome hypothesis" proposes that the surge of chronic disease in Western societies is due, at least in part, to the loss of bacterial diversity (LLoyd-Price et al). What spurned this disruption in the gut microbiomes? A low fiber diet compounded by excessive consumption of fat and processed sugars.

 

The Ideal Gut Microbiome

Do healthy individuals all share similar bacteria along their digestive tracts?

If so, would it be possible to populate unhealthy individuals with these healthy bacteria?

Alas! There is tremendous bacterial variation among the guts of healthy individuals.

"Early research into the ecology of the microbiome sought to identify a 'core' set of microbial taxa universally present in healthy individuals who lack overt disease ... but studies of ecological diversity among healthy individuals revealed sufficient variation in the [composition] of the microbiome to rapidly render such a hypothesis unlikely... Characterizing a 'healthy' microbiome as an ideal set of specific microbes is therefore no longer a practical definition" (Lloyd-Price et al).

So, a new hypothesis was born.

The prevailing theory is now that of a "functional core," a set of key metabolic functions rather than set of bacterial species. These functions are provided by different organisms in different individuals (Lloyd-Price et al). Unhealthy individuals lack bacteria that can perform specific functions rather than lack a specific species of bacteria.

What causes certain individuals to be colonized with a certain type of bacteria? Possible causes for inter-individual variation of microbiomes include:

  • Genetics
  • Early life exposures
    • Mode of birth
    • Source of nutrition
    • Antibiotic exposure
  • Geography
  • Diet
    • Western: High fat, High sugar, low fiber
    • Plant-based high fiber
  • Medications
    • Antibiotics
    • Acid reducers (Proton pump inhibitors, H2 blockers)
    • Chemotherapy

Interestingly, it seems that "species were likely stable over decades if not for an individual’s entire lifetime as evidenced by species shared with adult family members but not with unrelated individuals" (Shreiner et al.).

Although these species are stable over time, it's not only possible, but rather very easy, to alter the gut microbiome. The most efficient way to manipulate the bacterial species of the gut is through diet.

Stay tuned to learn about strategies to optimize the gut microbiome through diet.


Resources

Blustein, J., and Liu, J. (2015). "Time to consider the risks of caesarean delivery for long term child health". BMJ. 350:h2410.

David, Lawrence A. et al. "Diet rapidly and reproducibly alters the human gut microbiome" Nature. 23 January 2014; 505(7484): 559–563.

Gorbach, Sherwood L. Medical Microbiology. Chapter 95 "Microbiology of the Digestive Tract" Galveston 1996.

Heiman, Mark L. and Frank L. Greenway. "A healthy gastrointestinal microbiome is dependent on dietary diversity" Molecular Metabolism. 2016.

Jayasinghe, Thilini N. et al. "The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation" Frontiers in Cellular and Infection Microbiology. 19 February 2016.

Jumpertz, R. et al. "Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans". Am. J. Clin. Nutr. 2011. 94, 58–65.

Lloyd-Price, Jason and Galeb Abu-Ali and Curtis Huttenhower. "The healthy human microbiome" Genome Medicine. (2016) 8:51.

Mueller, Noel T. et al. "The infant microbiome development: mom matters" Trends Mol Med. Feb 2015; 21(2):109-117.

Perlmutter, David. Brain Maker. New York City, 2015.

Shreiner, Andrew B. and John Y. Kao and Vincent B. Young. "The gut microbiome in health and disease" Curr Opin Gastroenterol. 2015 January; 31 (1): 69-75.

http://missinghumanmanual.com/?tag=gut-flora