Thursday, February 6, 2014

The Human's guide to being Human: Your microbiome

While all biological functions occur through gene/environment interactions, most life on the planet is not possible without some form of assistance from a different form of life.  Most plants could not reproduce without pollination by insects and therefore they would not exist today without a little help from their friends.  This type of symbiosis is not reserved only for members of the plant kingdom, members of the animal kingdom, including humans, require some assistance too.

I'd like to begin this blog with a couple of questions.  What do termites eat?  If you're like most people, you know the answer to this question is wood.  However, if I were to tell you that termites are incapable of digesting wood, you may become a little confused.  The truth is, termites consume wood and as it makes it's way through their digestive tract, microbes found within their digestive tract break down the wood in to something termites can use to perform their every day functions(1).  Despite lacking the enzymes capable of breaking down wood in to something that is useful to them, termites are able to consume wood and get something out, but only with the help of bacteria capable of breaking it down first.

For my next question, I'd like to ask you if the diet of Gorillas is high in carbohydrate or high in fat?  Gorillas typically consume large amounts of fiber, a carbohydrate, as well as some fruit, also high in carbohydrate.  Since gorillas don't eat canola oil and aren't seen tearing apart other animals for food, it seems logical that a gorilla diet is a high carbohydrate diet then, right?  Not so fast.  Similar to the microbes found in the gut of the termite, microbes in the gut of gorillas break down fiber that they can't digest in to short chained fatty acids that the gorillas can absorb and use for energy.  All tolled, including fiber as a carbohydrate, Western Lowland Gorillas consume 84% of their diet in the form of carbohydrate.  However, once that is acted upon by the microbes in their gut, almost 60% of what enters their circulation is fat(2).  Without microbial fermentation of this non-digestible fiber in their gut, Gorillas would not have access to more than 57% of the calories they consume.  In other words, they could not exist without these microbes.

In humans, upwards of 1000 different species of bacteria live in the gut.  In addition to the gut, these bacteria can be found anywhere the body is exposed to air including the skin, mouth, eyes, and nose.  It may not seem intuitive that the digestive tract is exposed to air, but in actuality the digestive tract is a tube open on both ends, the mouth and anus.  In other words, it is not a part of your internal environment, it is actually an interface between the external environment and your internal environment, much like the skin.  Bacteria that reside in the gut perform a host of functions including digesting fibers we can't use in to short chained fatty acids that we can, training our immune system, regulating the integrity of the intestinal wall, manufacturing vitamins, and helping transport minerals just to name a few.

The collection of bacteria found within your gut is often referred to as your microbiome.  It is estimated that there are 100x more genes in your microbiome than there are genes within your cells.  In other words, from a biological function perspective you are more bacteria than human.  While all of the above mentioned functions are beneficial to us, the gut is not a sanctuary for good bacteria, bad bacteria can also reside there.  Depending on what you eat and the microbes you are exposed to, any number of good or bad bacteria can take up residence in the gut and perform their biological functions.

In the case of good bacteria, there is typically some benefit to the host in them being there.  Bad, also called pathogenic, bacteria tend to cause problems by either activating the immune system or secreting toxins directly in to the host.  In a way, your gut is like the petri dish mentioned in my last article on how cells work and the bacteria are merely vehicles for the genes that they contain since all biological functions are a product of gene/environment interaction.  By filling the petri dish with "food" that benefits a certain type of bacteria, you are effectively altering the genome found within that petri dish, in this instance your gut.  In this way, your microbiome is actually a more adaptable part of your total genome.  While your coding genes are fixed from birth, and your epigenome can change but over longer periods of time, your microbiome can change relatively quickly based on the type of food that's available.  In fact, a recent study showed that switching from a mixed diet to an all meat diet can cause the microbiome to change significantly in as little as 2 days(3).  Stress and sleep are also believed to impact the microbiome as would anything that directly affects either one.

Our microbiome is developed relatively early in life and changes as we age.  When we are born, we are exposed to the vaginal flora as we exit our mother's birth canal.  Those who are born via C-section do not get this exposure because they are removed via an incision in the stomach, which could lead to health issues much later in life.  Breast milk is another way we get exposed to beneficial bacteria early in life, so those who are not breast fed are at a further disadvantage in developing a healthy microbiome.  As we are able to crawl and interact with our environment as babies and toddlers, we also expose ourselves to more bacteria that will become part of our microbiome.

The hygiene hypothesis postulates that one of the reasons we have seen an increase in allergies and autoimmunity is because our focus on preventing children from ever coming in to contact with microbes from the environment prevents the immune system from developing properly.  There is evidence that there is something to the hygiene hypothesis as children raised on farms or with pets are less likely to experience allergies or autoimmunity.  Furthermore, the microbiome has been implicated in a range of health problems from autism to depression to obesity so there is the possibility that the microbiome is responsible for multiple areas of development, not just the immune system.

Even once you've entered adulthood, the microbiome will continue to change throughout life.  Combined with changes to the epigenome, the microbiome can dramatically change your health.  Studies in identical twins show that the same coding genes put through different environments can yield completely different outcomes.  There are identical twins where one is obese and one is lean.  There are identical twins where one dies of cancer and the other never gets the disease.  These changes can only come about through a change in the environment in which the genes are exposed to since the genes are identical.  We can adapt to a wide variety of environments, and this flexibility is afforded to us by the epigenome as well as the microbiome.

An interesting aspect of the microbiome that bears mentioning is that the appendix may be a reservoir for all of the types of bacteria that make up our microbiome.  When an infection of some sort occurs in the digestive tract, the colon pulls water out of circulation which causes diarrhea, a flushing of the digestive tract that removes both good and bacteria.  Then, based on the types of foods you eat, you will begin repopulating your colon with bacteria that were hiding in your appendix that make their way out and in to the colon where non-digested food arrives.  This is just a hypothesis, but it certainly makes me relieved that I still have my appendix and wasn't one of the people who had appendicitis and convinced it was useless, or more "junk" so to speak.

If we look at the traits of the 3 parts of the genome, we can see that each affects change differently.  The microbiome allows you as an individual to adapt to the environment quickly based primarily on the type of food that is available.  For example, many of the traits that the microbiome can affect deal with metabolism and the ability to store and use nutrients.  Quite a bit of the research I have been looking at recently leads me to believe that the microbiome likely helps us adapt to changes in the seasons in many ways, particularly by altering insulin sensitivity and increasing or decreasing metabolism.  It does this as the types of foods available from season to season change, and the types of foods we consume allow the proportions of different strains of bacteria found with in our microbiome to change as we provide a different environment within our inner "petri dish".  This is why a diverse array of different bacterial strains within our microbiome is important, it allows us to adapt to a wider variety of environments.  Our metabolic flexibility is largely dictated by our microbiome.

The epigenome allows an individual to become better suited to some aspects of the environment that are constant, but is able to change when the environment changes and becomes constant in another way.  Coupled with the microbiome, the epigenome likely has huge implications on your health and how you function from day to day as both can make you better at certain things based on how the environment interacts with these aspects of your genome.  You are, however, constrained by your coding genes.  You are not going to develop the ability to make an enzyme you've never been able to make.  Looking back at the termite at the beginning of this blog, if the termite were to somehow lose the microbes within it's microbiome that help it digest wood, it would be curtains for the termite.  In this way, the environment that your ancestors evolved in is also pretty important.

If you truly think about it, evolution is happening at all 3 levels of your genome.  Your microbiome is evolving based on the food you put in to your body, your cells are evolving as the microbiome changes the inputs to the epigenome which changes the inputs to your cells leading to different outcomes, and the human species as a whole is adapting as these other parts of your genome interact with the coding genes.  Furthermore, all 3 aspects of your genome allow you to adapt to the environment that you are in, in either a good way or a bad way.  With all of this talk about evolution and adaptation, it seems that a talk about evolution by natural selection is in order for the next blog.

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