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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