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In 2003, when University College Cork (UCC) set up a pioneering research centre to study the interaction between human health and the microbes in our body, the field was in its infancy.
The term “microbiome”, which describes the trillions of bacteria resident inside each of us, was not then in common use and UCC came up with the ungainly name of the Alimentary Pharmabiotic Centre for its institute.
The growth of what the Irish university now calls its APC Microbiome Institute illustrates the flowering of a field that arguably represents the greatest advance in scientific understanding of the human body so far this century.
“We were sure 13 years ago that this would become a huge new area of human biology — and so it has proved,” says Fergus Shanahan, UCC professor of medicine and APC director. “The number of research papers in the field has grown exponentially since we started.”
The APC now has 300 staff and is working with 22 partner companies in the pharmaceutical, biotechnology and food industries on 26 microbiome projects.
A typical adult hosts about 100tn microbes, mainly in the gut but also on skin, in the mouth, nose, genitals and elsewhere. They account for about 2 per cent of body weight. The vast majority of the hundreds of bacterial species in the human microbiome are benign, and indeed essential for health.
As research has uncovered more evidence about the biological role of the human microbiome, not only in digestion and metabolism but also in less obvious areas including immune response and even behaviour, so companies have piled into the field.
David Cox, healthcare analyst at UK stockbroker Panmure Gordon, notes the commitment of Nestlé, the Swiss food company, to microbiome research. “Products could be approved quickly via the consumer food supplement route in the first instance, before being reformulated as more potent pharmaceutical products,” he says. “Nestlé could really help this cause for smaller players through its commercial reach.”
UK companies active in the field include 4D Pharma in Leeds and OptiBiotix in York. In the US, Second Genome, based in San Francisco, has raised $59m from investors for microbiome research. And Seventure Partners, one of France’s top venture capital companies, has raised €160m for an investment fund focusing on the microbiome.
Prof Shanahan envisages three broad applications for microbiome products. The first is directly improving the composition of gut bacteria in people with impoverished microbiomes. Probiotic and prebiotic nutritional supplements do this gently by nourishing existing microbes or by adding new ones. A more drastic option is a faecal transplant: moving stool material from a person with a healthy microbiome into a patient who needs a bacterial boost.
Clinical trials show the procedure can help those suffering from clostridium difficile infection, a bowel infection. But, apart from the “yuck factor”, this is not a standard treatment and can be hit-or-miss in its effects. “We’re trying to develop an artificial stool to replace faecal transplants,” says Prof Shanahan.
Scientists at the Wellcome Trust Sanger Institute in Cambridge, England, have grown and catalogued 130 different bacteria from the human gut. Their aim is “to create a pill containing a rationally selected, defined mix of bacteria, which could be taken by patients and replace faecal transplants”.
The second application is to use the microbiome for discovering new drugs, especially much-needed antibiotics. The evolutionary arms race between bacteria leads to production of molecules that one species can unleash to kill another as they compete for resources in a particular ecological niche.
Most antibiotics prescribed today are based on these molecular weapons derived from soil bacteria. But researchers expect our internal microbes to provide a rich new source. In July, for example, a team from Germany’s University of Tübingen reported the discovery of a powerful new antibiotic called lugdunin secreted by nasal bacteria. Cork’s APC has identified 20 potential new antibiotics from the microbiome.
Third, the composition of the microbiome is a diagnostic indicator for some diseases. It may change, for example, in the early stages of colorectal cancer and other gastrointestinal disease.
However, Jaqui Hodgkinson, a vice-president at the life sciences division of Elsevier, part of the information and analysis provider RELX, warns that the huge volume of complex data involved in microbiome analysis poses a serious challenge. “With this complexity, comes the possibility of a huge margin of error,” she says. “While there is already a lot of published data on microbiomes, some of it may not be useful at all, dependent on the context and organism used in a study. It is already very clear that the microbiomes of humans are incredibly complex and variable.”
Regulators too face challenges. “Microbiomes could ultimately show more promise than existing therapeutics that try to target change in human cells,” says Dr Hodgkinson. However, learning which changes will have the most chance of therapeutic success will be “essential in making microbiome analysis usable in research and development”, she adds.
Steve Arlington, who chairs the Pistoia Alliance, which promotes R&D among life sciences companies, agrees. “Understanding microbiomes could be as big a leap forward in medicine as unravelling the human genome.”
He adds that the challenge lies in unravelling massive data streams that currently have no agreed standards. “These are exactly the types of things that the pharma industry will collaborate on, as we need a common language to drive forward innovation.”