Realising the potential of the microbiome

Big pharma and venture capitalists alike are increasingly keen to understand and exploit the functions of genetic material of the microorganisms in the human body. More than 100 trillion microorganisms live in the gut, mouth, skin and other mucosal surfaces, providing a range of beneficial processes that could help medical advances. Antonia Twiston-Davies explains the latest developments.

The human microbiome is becoming increasingly important across the life sciences industry. Understanding this 'organ' has the potential to change how we treat a range of diseases and illnesses, in particular gastrointestinal (GI) diseases and related cancers. With this potential now much more widely understood, a number of large and smaller pharma companies have entered the market in the past few years.

While much of the original work has come from academia through initiatives such as the Human Microbiome Project, the commercial sector is now increasingly becoming involved. Johnson & Johnson (J&J) has been particularly active and has worked to forge a series of early-stage research alliances. January 2015 saw them partner with Vedanta Biosciences in a deal which will see J&J pay an undisclosed initial fee and as much as $241 million for Vendanta's mix of bacteria from the Clostridia subspecies that could be used as a treatment for Crohn's disease and ulcerative colitis. This follows a deal in 2013, in which J&J committed undisclosed upfront and future milestone payments to Second Genome for the programme focused on ulcerative colitis, a chronic condition in which the colon becomes inflamed.

In addition, Pfizer announced a collaboration with Second Genome in 2014, and Novartis and Roche have research teams active in this area.

The venture capital community has not been slow to spot the potential of the microbiome. The French venture capitalist company Seventure recently announced it had closed a new fund, Health for Life Capital, focused on four areas, one of which is the microbiome.

"Since 2008, we have noticed a steady growth of interest in the microbiome," said Isabelle de Cremoux, President and CEO at Seventure Partners, adding: "I expect to see more and more deals in this area, with Seventure being one of its main drivers."

At the same time, both medical device and diagnostics companies are entering this space. While the pharma companies are working on new treatments, there is a significant need for both diagnostic and research tools to investigate the role of the microbiome in health and disease. For example, Origin Sciences has launched a sampling device to assist in the standardised collection of the gut microbiome, while Paris-based Enterome is developing personalised tests and companion diagnostics to detect dysbiosis of the human gut microbiome.

Sampling methods

There have been vast improvements in how research in the area of GI diseases and related cancers is conducted. Currently, the most commonly-used gut sampling methods are stool sampling, rectal swabs and mucosal biopsy. Each of these has its own limitations and the storage and processing of samples all impact microbiota analysis.

Stool samples are convenient and low-cost, but they do not fully replicate the mucosal-associated bacterial profiles. In addition, stool samples are usually taken by the patient at home rather than immediately in the clinic. This can reduce compliance as some patients do not like handling stool samples. There are also risks of contamination during collection, delay in freezing the sample, variations in home freezer temperatures, and thawing during transport to the laboratory. Compelling evidence suggests that these factors may introduce sample variation large enough to compromise microbial diagnostics.

A biopsy of the intestinal mucosa would produce a standardised sample containing mucosally-adherent bacteria, although the bowel preparation required pre-biopsy may affect the microbiota profile. This sampling method is also invasive, expensive, time consuming and produces a very small sample which is difficult to process. Rectal swabs can be taken immediately in the clinic and stored in a standardised way, but the amount of material collected is considerably smaller than other methods, limiting its use in research.

There is a clear need to develop a sampling method that collects mucosal samples to adequately characterise the complex microbiota of the colon. It is also important to develop a standardised collection method and DNA extraction technique.

A prerequisite for using microbiota analysis as a clinical tool is efficient and consistent sampling and sample preservation. An important factor in this regard is the influence of sample handling and the effect of intestinal preparation by bowel cleansing on composition of microbiota in stool and the mucosal layer of the colon. An ideal sample type for use in routine diagnostics should be easy to obtain in a standardised fashion and reflect the microbiota in situ.

Fortunately, there are now several new tools being developed. Origin Sciences has produced one incorporating a nitrile membrane, which is inserted into the rectum via a standard proctoscope and inflated to make contact with the rectal mucosa. The membrane is then deflated and retracted into the device prior to removal from the patient, with the sample retained on the inverted membrane. It can be stored frozen or a suitable buffer added to preserve the material for subsequent analysis.

Micropharma has developed an ingestible medical device which can sample the mucosa at pre-determined locations throughout the GI tract, including the small intestine.

Despite its relative infancy, research into the human microbiome is becoming an increasingly important area, with significant sums being invested in both new treatments and new tools for research and diagnosis. While this is a complicated and difficult-to-research area, these new tools and techniques are making it possible to use the microbiome to develop effective new treatments for a range of GI diseases. Microbiome research may be in its infancy, but early indications are that it will grow to a significant sector, with not only the ability to treat directly-related illnesses, but also to impact more widely on human health.

About the author:

Antonia Twiston-Davies works at Origin Sciences as a Project Manager, working on commercial and scientific projects. Her work supports scientists and investors in creating successful companies, and ensuring successful routes to market. She studied Cancer Biology and Immunology at the University of Bristol.