Tuesday, 16 July 2013

What do you think you are? (post 1 of 2)

You may consider yourself human, made up of human cells doing their human thing. However, this isn't the complete story. An average human adult is made up of roughly 10 to the power 13 cells (that's 1 followed by 13 zeros). While this is a fairly large number, it only accounts for 10% of the cells that make up a human body. A remarkable 10 to the power 14 bacterial cells and other microbial cells account for the remaining 90% of the cells that make us what we are. It may be better to consider humans as a super-organism, an ecosystem made up of human cells, bacterial cells, and many other forms of cellular life (and viruses). 99% of the genetic material within the human super-organism is microbial, not human, which some refer to as our "second genome." These microbial co-habitants aren't simply freeloaders either; it is becoming increasingly apparent that this "second genome" may be playing just as much, if not a greater, role in human health and disease. Additionally, while our genome is fixed, we may be able to shape the microbiome (all of the microbes that call us home) in a therapeutic guise, giving new avenues for treatment of diseases as diverse as obesity, immune-related and mental. Over the next couple of blog posts (there’s a lot to say so I’ve divided it into two) I'd like to discuss with you some of the evidence for how important the microbiome is and the importance it may be playing in a handful of diseases. 

The human digestive tract
While bacteria can be found all over humans, one of the largest concentrations of our microbial tenants can be found in the gut. To start with the most graphic of examples for how important the microbiome is let us look at fecal transplants. A reoccurring theme through this set of blog posts will be the fact that antibiotic use damages our bacterial inhabitants. Obviously we need antibiotics to treat dangerous bacterial infections, but they do have the side effect of depleting the beneficial bacteria, especially when broad-spectrum antibiotics are used. It has been observed that infection with antibiotic resistant C. difficile is common following courses of broad-spectrum antibiotic treatment for other diseases. C. dif. infection is largely a hospital acquired infection and can lead to death. Recently fecal transplants have been successfully used in C. dif. patients and these have been shown to lead to recovery from the infection which antibiotics can do very little for. The fecal transplant, or fecal bacteriotherapy as some refer to it, introduces a whole range of new bacterial species into the patients gut to replace those damaged by the original antibiotic treatment. These new species are able to grow and outcompete the harmful C. dif., allowing recovery. Clearly having an intact microbiome is important in this disease.

A clump of E. coli in the gut imaged
by scanning electron microscopy
The importance of our bacterial self can be seen in less graphic ways also. One good way to study the microbiome is to look at babies, and much of our understanding has come in this manner. Prior to birth, babies have essentially no microbiome. At birth however they are inoculated with numerous bacterial species and continue to develop their microbial populations until about the age of 3, when the microbiome becomes largely set. Natural birth is a very good way to inoculate a newborn with the necessary bacteria, as it's a fairly messy process. A far cleaner birth is achieved through caesarian section, a procedure done in a largely sterile manner. Studies of babies born through the two different methods have shown that there is, as you may expect, a large difference in their microbiomes. Babies born through C-section have a microbiome that, to a large extent, resembles the skin bacterial populations of the mother, where as babies born naturally have microbial populations resembling that of the mothers gut and vaginal bacteria. Having these different populations seems to have some consequences with certain studies suggesting that C-section babies have a higher incidence of asthma, allergy and autoimmune disease. These diseases are thought to be down to the altered microbiome. There is in fact an on going trial in which C-section babies are being inoculated with vaginal secretions to ascertain the true importance that the altered microbiome is having to health and disease. 

Bifidobacterium imaged by scanning electron microscopy
Infants have also provided further insights into the importance of our microbiome, this time from an evolutionary point of view. Breast milk is the only food source that is shaped by evolution, so the fact that it contains complex carbohydrates that babies are unable to digest, and therefore make use of, was for a long time a mystery. Why would resources be wasted putting sugars into milk that provide no benefit for the baby? Or alternatively, why have we not evolved a mechanism to digest and use these sugars? It was eventually discovered that even though we humans lack the ability to use the carbohydrates, a bacterial species in the gut known as Bifidobacterium are very capable of putting them to good use. Providing these bacteria with the sugars they need allows them to rapidly grow and become one the major constituents of our gut microbiome. Filling the gut with harmless Bifidobacterium means there is a reduced chance for other bacteria to grow, protecting us from colonization by pathogenic bacteria. Bifidobacterium are also important in another respect that I will get to in the next post. Mother's milk has been shaped by evolution and this process has resulted in the inclusion of sugars that are there simply for the benefit of a bacterial species found in the gut of babies. Clearly evolution has favoured the growth of the microbiome in this manner, once again showing how important our bacterial inhabitants are.

I shall end this post here so as not to take up too much of your time. The second half will continue on a similar theme looking at another partly evolutionary based argument for the importance of our microbiome before moving on to look at diseases linked to disruption of the microbiome. Be sure to come back for the concluding part…

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