The Microbiome: Brave New World for Biotech and Policymaking

The Microbiome: Brave New World for Biotech and Policymaking

New Knowledge Portends Future Changes in Medical Diagnostics, Therapy and Research

The first phase of the National Institutes of Health's Human Microbiome Project  that ended in 2012 provided science a much better understanding of the extraordinary number, diversity and potential importance of microorganisms that inhabit the human body. Phase two of that project is now creating the first integrated database of biological properties to facilitate more accurate studies of the relationship between that "microbiome" -- or internal constellation of organisms -- and human health and disease.

During the first phase of NIH's
Human Microbiome Project,
researchers discovered more
than a thousand different
kinds of bacteria living sym-
biotically inside humans.
There is growing evidence
that these colonies of org-
anisms play significant and
previously unknown roles
in human health.

Not surprisingly, the biotechnology industry is keeping the closest eye on these findings and has already begun developing therapies that may alter the microbiome in ways that effect human health. Business start-ups are seeking to capitalize on what the microbiome can teach the medical profession: For example, could the makeup of their microbiome explain why some patients respond better to particular drugs than others? These companies are facing a raft of challenges -- not the least of which is how policymakers are likely to regulate the new field which many predict could revolutionize some areas of medicine.

'A sea change in how we think'
One of those is entrepreneur Peter DiLaura, CEO of South San Francisco-based Second Genome, an economics alumnus of the University of Pennsylvania's Wharton School. "We have 100 trillion bacteria that we are all carrying around with us and that play a critical part in things like our immune system and the way we process energy," he said. "In the past, we have been focused on addressing the pathogenic component of bacteria. But in reality, there's a tremendous benefit of this bacterial community in our body. That's really an important sea change in how we think about health."

Second Genome was founded in 2009 with technology developed at Lawrence Berkeley National Laboratory that allows scientists to identify microbes and analyze their DNA. "We now have a capacity we never had before to interrogate and understand this really complex population of bacteria and how this bacteria interact with the host -- the human biology," DiLaura said.

Bacterial secretions
DiLaura's company is studying the substances that bacteria secrete, such as proteins and metabolites, with the goal of developing drugs to manipulate the microbiome and therefore change the course of particular diseases. "In disease situations, there's something wrong with how the microbiome and the host are interacting," DiLaura says. "We believe the biological reactions between the microbiome and the host can either be inhibited or activated in order to improve certain disease states."

Peter DiLaura, CEO of Second
Genome: 'The biological react-
ions between the microbiome
and the host can either be
inhibited or activated in order
to improve certain disease
states.'

Second Genome is still in the pre-clinical stage -- which means that the company has not yet identified drug candidates that it wants to test in people -- but it has identified a few research priorities, including inflammatory bowel disease and Type 2 diabetes, DiLaura said.

In 2013, DiLaura said, Second Genome formed a research collaboration with Janssen Biotech, a unit of pharmaceutical giant Johnson & Johnson. The deal is centered around advancing drug targets to treat ulcerative colitis. J&J's interest won't just help Second Genome advance its science, DiLaura notes; it also marks an important stamp of approval to the entire microbiome field. "In any emerging area of science, it's exciting when the pharmaceutical industry recognizes its importance to their work in a particular disease area. As an early-stage biotech company, we have to collaborate on innovation."

900-patient study
In another just-announced joint project with Pfizer and Massachusetts General Hospital, Second Genome plans to launch a 900-patient study aimed at comparing how the microbiome makeup of obese individuals may differ from that of normal-weight individuals.

Venture capitalists appear enthusiastic about such Microbiome prospects: Second Genome has raised $11.5 million from Advanced Technology Ventures, Morgenthaler, Wavepoint Ventures and individuals, including co-founder and biotech serial entrepreneur Corey Goodman. Other well-funded startups in this space include Vedanta Biosciences, Seres Health, Microbiome Therapeutics and ViThera Pharmaceuticals.

One of the leading academic researchers in this new field is Gary Wu, a gastroenterology professor at Penn's Perelman School of Medicine, who says the early evidence is pointing to a range of possible roles for the microbiome in treating disease. "The whole notion is that if you could make the microbiome look healthier, in fact it could be used to treat disease or prevent the development of disease."

Gary Wu, MD, Gastroenter-
ology Professor at the Univer-
sity of Pennsylvania's Perelman
School of Medicine, and Chair
of the scientific advisory board
of the American Gastroenter-
ology Association's Center for
Gut Microbiome Research
and Education.

Digestive and metabolic diseases
Manipulating the microbiome may prove useful beyond digestive and metabolic diseases, Wu adds. "Allergic diseases, for example, have a genetic component -- our genome predisposes us -- but also there's an environmental effect. Microbes are all over the place. There's evidence that microbes in the gut may play a role in autism spectrum disorders through the production of exotic small molecules. There's evidence that the microbiota can transform certain dietary constituents into a gas that may accelerate coronary vascular disease. Then there's the skin microbiome, which has a role in the development of psoriasis and in wound healing."

Wu chairs the scientific advisory board of the American Gastroenterology Association's Center for Gut Microbiome Research and Education, which acts as a clearinghouse for information and guidance on research in the field. One of the group's priorities is to help shape the regulatory pathway for microbiome therapeutics -- a pathway that is still largely undefined, Wu says.

Unregulated products, unsubstantiated claims
Part of what complicates the regulatory picture is that there are already nutritional products on the market that target the microbiome, and they are largely unregulated, at least from a medical standpoint, Wu says. They include "prebiotics," which are dietary fibers that purport to promote the growth of healthy bacteria in the digestive tract, and "probiotics" -- live bacteria found in yogurt and other dairy-based foods as well as in pills sold over the counter. Probiotics are pitched as digestive aids, perhaps most famously by Dannon and its brand Activia.

"These probiotics, in general, tend to be single or maybe two or three organisms. We don't really have any evidence they actually set up shop in your intestinal tract after you swallow them, because they're not resilient," Wu says. "The opportunity is to use genomics to target disease based on the biology of these organisms. In the future, I think there's going to be a lot of interest in developing designer populations of microbes."

Regulatory puzzles
At that point, the Food & Drug Administration and other regulatory bodies will have to step in, because such products would be marketed as drugs to treat diseases. "A complex microbial community is a live community that can change over time. We all believe that for the safety of people who receive these types of treatments, there should be certain standards," Wu notes. "It's a challenge, because this is a very new area for regulatory agencies."

For example, these agencies will need to define whether a consortium of microbes constitutes a "biologic" (large-molecule) drug or a chemically based drug, or some combination of the two, because that definition will determine its regulatory path. "And how do you define it if it's going to change over time?" Wu asks. "There are many questions that I think the FDA and other regulatory agencies still haven't answered for themselves. So any company that's working in this space has to work collectively with the FDA to define the pathway forward."

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Arlene Weintraub is a New York-based journalist specializing in life sciences and technology. A former senior health writer at BusinessWeek, she has also written for Knowledge@Wharton, USA Today, US News & World Report and other major media outlets..