The Microbiome: Can New Sequencing Techniques Fast Track Therapeutic Discovery?

A true staple of modern pop-science, the age-old nature vs nurture debate is the bread and butter for many. However, what the Dawkins-clutching masses may not be aware of is that our bodies have a further phenotypic control mechanism. One which, quite frankly, is a little bit gross. The human microbiome or microbiota is the name given to the multitude of bacterial colonies that exist within us. The way that these colonies grow and interact plays a part in an immense number of bodily functions and both our risk of and response to diseases. From absorption to autism and sleep to semen, the little colonies that reside inside you control you in ways you may have never realised.

The most prevalent area of bacterial activity is the gut – this is known as the human gastrointestinal microbiota or the gut flora. Like the microbiomes throughout your body, the gut flora has a number of functions: particularly notable in this is immune system regulation. The bacteria in your gut respond to the chemical markers that control immune reactions and up-/down-regulate them to optimise the immune response. 

Image Credit: Oxford Images

That’s not all; Paul Patterson and Sarkis Mazmanian described the role of bacteria in autism development in experiments undertaken at Caltech in 2001. If a pregnant woman acquires a serious infection (e.g.: flu or measles) their children have an increased risk of developing autism or schizophrenia. This happens because the viral infection leads to the children having an abnormal microbiome and abnormally “leaky” guts. This means that chemicals from the gut leak out of the gut, travel up to the brain (in the blood) and stimulate the behaviour that is characteristic of autism spectrum disorders and schizophrenia. The bacteria are also reported to alter gene expression in individuals which further leads to the expression of autism spectrum disorders. Peterson emulated this effect in mice. He administered a bacterium called B.frag (Bacteriodes fragilis), an important bacterium that makes up part of the normal human microbiota. After administration, the autism spectrum characteristics disappeared. This is because the bacterium increased the diversity of the mice’s microbiomes and reduced the effect of their “leaky” gut.

This example is very good in illustrating the fact that, aside from the presence of the bacteria, the composition of the bacterial colonies plays a major role in regulating the body. The microbiome is therefore extremely complex – that’s why you don’t see many microbiome-based therapies on the market.

Regardless, there are many people working to produce therapeutics that utilise the human microbiome. Key to this is understanding the interactions between bacterial colonies. A novel sequencing method called themetagenomics has recently been derived by researchers at Drexel University, Pennsylvania. It builds on current sequencing techniques, which are able to describe the various bacteria in the microbiome and indicate how the colonies interact with each other. The technique utilises machine learning algorithms to study populations of bacteria and derive how they interact.

This is particularly useful in understanding how the biome changes with time, thus describing how microbial changes correlate with changes in the body. Understanding these changes will help us understand how cohabitation correlates with disease. This services the ultimate aim of producing diagnostic and possibly therapeutic methods relating to various diseases.

The academics at Drexel tested their sequencing technique against the current diagnostic techniques for Crohn’s disease. Thematagenomics proved to be as accurate but much faster than the standard techniques – it took minutes rather than days. This discovery has been hugely significant in bringing the microbiome into modern healthcare practice. Furthermore, the group has made the thematogenic analysis tools free for public access, with the aim of developing the science further towards therapeutics.

The future for microbiome therapy does look bright, with second phase clinical trials for diseases like irritable bowel disease, Crohn’s disease and more approved or ongoing. These therapies centre around prebiotics, which involve administering bacteria with the aim of increasing the populations of beneficial bacteria; probiotics, which involve administering bacteria to change the makeup of the biome and its functional output; or bacteriophages, which kill certain bacteria in the biome to alter its makeup.

While these may be some way away from popular use, the science certainly does seem promising. Microbiome therapies may reach the market within the next five years.

This article was written by Harin Wijayathunga and edited by Hollie Marks.

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