The Age of the Microbiome in Drug Discovery
Over the course of the last century we’ve had the age of antibiotics, the genetic revolution, transplantation and immunotherapy, each of which ushered in a raft of new therapies dramatically improving human health. Now we enter the “Age of the Microbiome” in drug discovery, the scope of which potentially exceeds anything that has gone before it.1 We invited Dr. Andrew Johnson of the University of California to introduce us to this new frontier in a four part blog series.
There are two main reasons that the microbiome has got drug discoverers so excited. The first is that the microbiome represents a metaphorical rainforest of new biological compounds waiting to be discovered and brought to the clinic. Many target other microbes within the same ecosystem whilst others continuously interact with our own bodies in ways which can be either beneficial (in day to day life) or harmful (in the context of disease). These compounds and the bacteria which make them offer great therapeutic potential for diseases which have so far proven difficult or expensive to treat. The second reason which has brought the microbiome to the forefront is its ability to explain something which has baffled researchers and clinicians since medicine began. “Why is a drug so effective in one person and yet completely ineffective or even harmful in another?”. The answer, it seems, might well lie in the gut as the bacteria living there strongly influence how orally administered drugs are absorbed and metabolised. Some microbiomes let a drug pass by freely, others are required to activate it, and yet more may chew a drug up, turning it into something inactive or even damaging. So not only does the microbiome hold the potential to discover a raft of new drugs, but also to “re-discover” many existing ones.
OK, so that’s the future, but what does it mean for scientists, clinicians and the general public right now?
Scientists, we need to be getting to grips with the microbiome in our own research. The spectrum of diseases in which the microbiome has been implicated is growing at a phenomenal rate, including many cancers, inflammatory diseases, metabolic conditions, such as obesity, and even behavioural disorders such as autism.2, 3 In fact, if you’re working in vivo then it’s a safe bet that the microbiome is affecting your data. Remember those two mice that just didn’t respond the same way as the rest, or that experiment from another lab that you just couldn’t replicate? Well observations just like that initiated great microbiome discoveries published in Nature,4 Science,5 and Cell.6 Fortunately, advances in Next Generation DNA sequencing technology mean that adding analysis of the microbiome to your experiment is incredibly affordable and can be outsourced to dedicated service providers, such as these listed by Scientist.
For the rest of us the microbiome is a very personal affair. No two people have the same microbiome, not even identical twins7! So, as the world moves towards personalised medicine, the microbiome, along with your own genome, may soon be viewed as essential knowledge for a patient and their doctor to have. After all, they say knowledge is power and in the age of the microbiome your bacteria may well prove to be very powerful indeed.
- Gurwitz, D. (2013). “The Gut Microbiome: Insights for Personalized Medicine.” Drug Development Research 74(6): 341-343.
- Blumberg, R. and F. Powrie (2012). “Microbiota, disease, and back to health: a metastable journey.” Sci Transl Med 4(137): 137rv137.
- Hsiao, Elaine Y., Sara W. McBride, et al. (2013). “Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders.” Cell 155(7): 1451-1463.
- Henao-Mejio, J., Elinav, E., et al (2012). “ Inflammasome-mediated Dysbiosis Regulates Progression of NAFLD and Obesity.” Nature 482: 179-185.
- Markle, G. M. J., et al. (2013). “Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity.” Science 339(6123): 1084-1088.
- Elinav, E. (2012). “NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis.” Cell 145(5): 745 - 757.
- Turnbaugh, P. J., M. Hamady, et al. (2009). “A core gut microbiome in obese and lean twins.” Nature457(7228): 480-484.