The microbiome – the next big frontier in medicine

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The human ‘gut microbiota’ is the name given to the community of microorganisms living in the intestine, and the human ‘gut microbiome’ consists of the genes these cells harbour. These microorganisms include bacteria, viruses, fungi, protozoa and archae. Think of it as an ecosystem – like a rainforest.

This article was first published here.

Until relatively recently, the microbiome had been a largely overlooked area of science and medicine, mainly due to the fact that it comprises of so many organisms (trillions). This made it a very daunting task to study. However, recent advances in analytic DNA sequencing technology has allowed the scientific community to better study the these organisms and this in turn has led to tremendous growth in the collective knowledge of the human microbiome (Fig 1). Indeed, there is now a large body of research that shows that the microbiome exerts a powerful influence on our immune system, as well as many other key physiological and biological processes. Taken collectively, these data show that the microbes that live in our gut play a critical role in our health.

Fig 1: Number of studies with “microbiome” in the title and/or abstract. (Source)

Drugging the gut microbiome 

Changes to the composition of the microbiome are associated with a number of diseases, ranging from obesity and diabetes to Inflammatory Bowel Disease (IBD). In light of this, restoring a healthy microbial community through therapies that manipulate the microbiota offer an exciting novel therapeutic avenue.

There are a number of differing approaches and strategies being investigated by academic laboratories and companies. One approach is that of a Faecal Microbiota Transplantation (also known as FMT or a stool transplant) which involves the transfer of faecal material (poo) from a healthy person into the bowel of someone suffering from a disease. These have been shown in clinical trials to improve insulin sensitivity, and cure over 90% of patients that suffer from a bacterial infection called C.diff. In addition, there is emerging evidence that shows that FMT is a promising treatment option for IBD. Clinical trials are also underway investigating FMT as a treatment for Irritable Bowel Syndrome and obesity. Perhaps unsurprisingly, there are companies that are working on FMT, two of which are the American based OpenBiome and the Scottish biotechnology social enterprise that I lead – EuroBiotix CIC. 

Seres Therapeutics take a different approach. The company is focusing on synthetic/bio-engineered formulations of bacteria that is derived from human stool. The company’s lead product candidate, SER-109, is a oral formulation that contains spores from about 50 bacterial species. SER-109 showed strong promise in a Phase IB Trial, however, the drug showed no statistical superiority when compared to a placebo in a Phase II Trial. The drugs failure is a reminder of the complexity of the microbiome. It may be that SER-109 failed because there is something important about the full community of microorganisms in whole stool that is irreducibly beneficial. By bioengineering the stool, it may be that the important something is lost.

Although there are many competing theories in the medical literature, we don’t really understand why FMT’s work – we just know that they do. If SER-109 had been successful, I doubt that Seres Therapeutics would have been able to present an elegant and irrefutable mechanism of action for the drug. All things considered, further research is required to elucidate why the drug failed, as well as further research investigating how FMT works.

Other companies such as Enterome, Vedanta Biosciences and Second Genome are all taking small molecule based approaches to the microbiome and have entered into clinical trails with their lead candidates. I could go on, however there are far too many investigators and companies for me to exhaustively list in this post. The point I’m trying to make is that this is truly an exceptionally exciting field of science, and there are many companies trying to capitalise on the research.

What about big Pharma?

Big pharma have certainly taken notice of research into the microbiome. Janssen pharmaceuticals have probably been the most active, having established collaborations with Second Genome and Vedanta Biosciences, as well as establishing the Human Microbiome Institute (JHMI) as a new research platform.

Pfizer and GSK are also keeping a close eye on the field. Pfizer have announced a collaboration with Second Genome and GSK have announced research into the lung microbiome. In consideration of all of this research and development, many experts believe that it is only a matter of time before the field see’s its first high profile acquisition.

Conclusion and future perspectives

There is no doubt that the potential for the microbiome is great. This article has focussed on novel therapeutics, and has not touched on other exciting developments inmicrobiome based diagnostics and personalised nutrition.

In light of the great expansion in microbiome science and research, we can expect to see a great explosion in therapeutics and therapies. The question is not if, but when. At the present time however, it appears that good old fashioned faecal transplants are more effective than the bio-engineered approaches. That being said, faecal transplantation can definitely be improve upon, and at EuroBiotix CIC we have a number of research objectives that seek to refine and optimise the treatment for the patients that need it.

Eventually, I believe that the field will move to the construction of personalised bacterial cocktails. This would require a more in depth knowledge about what a healthy microbiome actually looks like, because at the present time, this is still somewhat of a mystery.

In conclusion, there are multiple microbiome based therapeutics that are nearing clinical implementation. Within the next two decades (some say decade) we will see a complete paradigm shift in the way that we interact with the bacteria that live inside us.

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