DISCOVERY: GENETIC MECHANISM AND MICROBIOME COLONISATION

New discovery shed light on a long puzzled vital mechanism of our body namely, how thousands of species of bacterias survive and thrive in our gut eco-system.

The gut is in an environment that is constantly changing , when we eat food and drink or even when we are under too much stress. Despite this constant change our gut is host to a variety of bacteria which thrive and survive in a stable eco-system.  As a matter of fact most mammals are colonized throughout there life with 100 trillion bacterial cells consisting of hundreds of microbial species. Researchers have long been puzzled by how these thousands of species do this, why certain bacterias thrive over others and more importantly the contributions of this enormous and diverse ecosystem to human health.

 

 

THE DISCOVERY:
A group of U.S researchers from the California Institute of Technology led by Prof. Sarkis Mazmanian identified certain genes as crucial to the diversity, concentration and type of bacteria in our gut.

 

Mazmanian research propose that the human genome "does not encode all functions required for health but rather that humans depend on crucial interactions with products of the microbiome" . In other words, those genes are said to nurture the environment in our gut, allowing a stable microbial colony to form where the Bacteriodes bacteria group seems to benefits the most from this.

Professor Mazmanian defined his goal as " to define the molecular processes evolved by symbiotic bacteria that mediate protection from inflammatory and autoimmune diseases."  A goal the could lead to further discoveries of just how these colonies work and to specifically understand the interaction of the beneficial immune responses promoted by symbiotic gut bacteria.

Amazingly, many of the 21st century disorders whose incidences are exponentially increasing in Western countries involve “a common immunologic defect found in the absence of intestinal bacteria."  Practically, this means research could be streamlined to the development of "natural therapeutics based on entirely novel biological principles." That in turn would achieve optimal balancing of microbial system for a better health and rectifying the changes linked to a few disorders such as IBS and some forms of autism.

 

From the Mice in the lab to the Human

The initial stage of this study used sterile (germ free) mice. In this variety of experimentation these mice were given Bacteriodes. The reason for choosing this bacteria group was due to the abundance present in humans. Also, from a practical point of view, It is easily cultured in labs, where most other gut bacteria are unable to grow outside of the human body. It can also be modified genetically, allowing certain mutations to be introduced and studied.

 

 

Using a single mouse, a variety of different bacteria species were used to determine whether these bacteria would fight for survival in the gut. Upon further observation it was found that the specific strains added were able to coexist quite peacefully in the gut of the mouse.However, there was a marked changed when a specific group, bacteroides fragillis, were used to colonize the mouse’s gut. The mouse was then injected with the exact duplicate of bacteroides fragillis. The test was to determine whether these exact same two groups could share the same host. Results showed that, even though the mouse already had this bacteria in its gut, the second addition of the same bacteria could not survive.

 

One of the author of this study, Dr. Melanie Lee, posed the question that, if we are aware that this environment is able to hold hundreds of bacterial species, why would there be any competition at all between the same species?

 

Hypothesis: Genetic Influence

In order to better explain these findings, Lee and her team came up with a fresh theory. It was referred to as the “saturable niche hypothesis” and was based on the argument that a single species can immerse themselves in a specific environment. This will efficiently block other groups within duplicate sets of species from being able to occupy that particular corner.

It was also observed that the saturation of that one specific group would not deter groups, which were related quite closely, from being able to thrive due to them having their own corner, or niche, within the gut. Imagine it as a neighborhood where mixed cultures share the environment but stay peacefully within their own ethnic group.

While utilizing genetic screening , the team was able to support their theory. It was during this screening that the genes, uncharacterized previously, were discovered. They also found that this set of  genes were not only a requirement for species specific colonization, it was also sufficient for the bacteroides fragillis set. This was later named “commensal colonization factors” or CCF, by the team.

 

 

Contact with Bacteria

Another important discovery was made by Lee’s team; the microbiota found in our gut could actually live in the lining of our gut. Lee went on to use cutting edge imaging in order to study the colonic tissue of these mice previously used. This revealed that there was a gathering of microbes residing in small pockets called "crypt" found in the colon.

By living in these pockets the bacteria is protected from a constant stream of the material which moves through out GI tract daily. Lee decided to put the CCF system to the test in order to determine whether this theory actually adjusted the colonization of bacteria within these pockets of the colon.

 

Researchers introduced bacteria which had been mutated and which did not fall under the CCF theory, into the colon of several sterilized mice. It was observed that the mutant bacteria that was introduced into the colon’s of the mice were not capable of colonizing these pockets.   Therefore, Mazmanian concluded that this "demonstrate for the first time that specific gut bacteria direct the development of the mammalian immune system and confer protection from intestinal diseases"

Professor Masmanian explains that there is something within that pocket, which is yet to be discovered, that the B. fragillis can utilize in order to get a firm footing by way of this system (CCF). It was a huge advance in this field, finding these pockets in the colon, which now shows that there is actual contact between the host and bacteria.

 

 

Masmanian observed that the Internal stability was indeed maintained during the scope of these experiments. He further pointed out that, while popular belief was that bacteria caused inflammation by connecting with the host, there was no real proof to back this up. Actually, the team feel that these pockets are a permanent residence of Bacteroides along with other microbe classes.

It does appear that the team’s research has brought to light an answer to the long standing mystery regarding how microbes can create and maintain a long term settlement.

 

The question was asked whether this stood for all other bacteria. Lee explained that only a small group of organism have been studied thus far. And while these are quite abundant, they clearly do not represent all of the organisms found in our digestive system.

The problem with this study

By testing the same researchers found other bacteria that do not hold the CCF gene, bearing the question of whether these organisms rely on the synergy between them and Bacteroides as a way to maintain their own settlements within the gut. The team explained that they believe Bacteroids are a foundation species, one that is needed in order for the ecosystem of the gut to be established.