Looking for a drug tailored to your DNA? Think precision medicine


60 second summary

  • The microbiome is sequenced by looking for variations in the same gene of different bacterial cells
  • Every disease has a different effect on the bacterial population inside the body
  • By screening and sequencing microbial communities diseases may be treated earlier and more thoroughly with personalised treatment

Are the treatments for diseases we use today really that effective?

Many of the conditions we suffer from in this are what we call multifactorial. This means that they are caused by a variety of contributing factors such as diet, genetics, exposure to pollution etc. In their best efforts, scientists try to manufacture a drug that will suit everybody- by which what is meant is the majority.

Every single person’s body’s reactions are unpredictable and it is difficult to tell who will be most touched by side effects. Therefore recently precision medicine is recently greatly increasing in popularity and demand- the ability to personalize a drug for your disease based on your lifestyle and your DNA brings with it a bounteous amount of opportunities.

Why should microbes be used in precision medicine?

The microbiome is one of the main areas focused on it personalized medicine research. This is because of its profound effects on brisk, short term changes in our health such as the common cold as well as chronic and serious conditions like diabetes and cardiovascular disease. Furthermore, as a result of the rapid advancements of technology, sequencing of a complete bacterial genome can be performed for under one hundred dollars on a lab bench. [1]

How to sequence a microbiome?

Distinguishing the quantity and species of microbes involves taking samples and looking for variations in DNA sequences called genes. Each microbe has a specific sequence so the more types of arrangment you find, the greater the diversity.

The science: Arguably, the most popular method to distinguish the presence of different microbes in an individual is via the 16S rRNA method. 16S rRNA is a gene coding for a molecule used in the production of a ribosomal subunit which is a structure used to form proteins in the body.[2]

How do scientists decide which gene/genes to sequence? There are hundreds!

The 16S rRNA gene used is highly conserved in bacteria meaning that it has been essentially unchanged throughout evolution- it is present in every single bacterium;[3] however it contains regions which are variable and unique to each species of microbe which allow each strain to be differentiated through sequencing.

To what extent do microbial communities vary in different diseases?

The importance of precision medicine in terms of the microbiome is that each disease differs in the way it alters the microbiome, and these differences can even be seen in divergent forms of the same condition. One example of this is Inflammatory Bowel disease (IBD) which affects over 300,000 adults in the UK[4]. It is characterized by abdominal pain diarrhea and cramps[5] which can be divided further with each subdivision presenting its own microbial differences.

The science: IBD divides into: Ulcerative colitis, intermediated colitis and Crohn’s disease

Each of these conditions can be split even further for instance Crohn’s disease into: Ileal Crohn’s disease and Colonic Crohn’s disease.Even at this detailed level of diagnosis population of microbes can be contrasting such as the former having significantly increased bacteria E. Coli compared to the latter.

Importance in sequencing one’s microbiome in terms of disease treatmant

Overlooking a persons microbial ecosystem can also be detrimental because bacteria can alter the efficacy of drugs. For example Paracetamol competes with chemicals produced by microbes and so its degradation in the body is hastened and less of its is available to be absorbed and used- this process differs from person to person which is why developing a safe threshold for medicine doses is hard.

The science: Bacteria in the large intestine produce a metabolite called p-cresol which is a product of fermentation[6]. It competes with Paracetamol in a reaction called )-sulfonation.

O sulfonation- formation of a covalent bond between an oxygen in a substrate and sulfo group.[7]

 This means that only some of the drug can actually be absorbed and used- the rest is broken down and excreted from the body by a process called glucorodination.

Concluding thoughts

Overall, sequencing a persons microbiome has huge future implications in preventative medicine and disease treatment and thorough scientific research is currently being conducted to unmask our gut bacteria’s potential.

[1] PMC. (2018). Microbiome at the Frontier of Personalized Medicine. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730337/ [Accessed 16 Jul. 2019].

[2] PMC. (2018). The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535273/ [Accessed 16 Jul. 2019].

[3] Medicine net. (2018). Medical Definition of Evolutionarily conserved gene. Available at: https://www.medicinenet.com/script/main/art.asp?articlekey=3344 [Accessed 16 Jul. 2019].

[4] Crohn’s & Colitis UK. (n.d.). About Inflammatory Bowel Disease. [online] Available at: https://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-diseasehttps://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-disease [Accessed 16 Jul. 2019].

[5] Wikipedia. (n.d.). Inflamatory Bowel Disease. [online] Available at: https://en.wikipedia.org/wiki/Inflammatory_bowel_disease [Accessed 16 Jul. 2019].

[6] Wikipedia. (n.d.). P-Cresol. [online] Available at: https://en.wikipedia.org/wiki/P-Cresol [Accessed 16 Jul. 2019].

[7] Royal Society of Chemistry. (n.d.). O-sulfonation. Available at: https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=MOP:0003559&MSID=c1ob06415k [Accessed 16 Jul. 2019].

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