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The unseen microbes that rule the world

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By: Jessica Hostetler, B.Sc.

The White House Office of Science and Technology Policy (OSTP) announced on May 13th, 2016, the formation of a National Microbiome Initiative (NMI). It is the latest in a series of scientific initiatives aimed at solidifying the legacy of the Obama administration, joining efforts aimed at curing cancer, delivering on the promise of personalized medicine, mapping the human brain, and developing new antibiotics. Why might this latest effort matter? The NMI has the potential to have a huge positive impact for human health and society, and it may prove to be one of the most productive of the programs initiated by the Obama administration.

Why microbes matter: a brief history of microbiome research

Microbiome research grew quickly on the heels of revolutionary advances in DNA sequencing technologies in the early 2000’s. These changes made sequencing DNA exponentially cheaper and faster than earlier technologies. Early work in the field of “metagenomics” aimed to understand the microbes present in a variety of ecosystems, starting with microorganisms in acid mines, wastewater, the human gut and the world’s oceans. Many species of bacteria will not grow in a laboratory setting or petri dish (in vitro), leaving researchers to try sequencing all the DNA from a mixture of organisms in these ecosystems. After the jumble of sequences were generated, scientists developed software to categorize DNA sequences and try to determine what kinds of microbes were present in the samples. The Global Ocean Sampling (GOS) project from the J. Craig Venter Institute in 2007 nearly doubled the number of known protein sequences at that time, pointing to potentially thousands of new biochemical pathways.

Scientists quickly expanded on this early work by integrating the knowledge gained from the study of microbes and applying it to human beings to understand the microbiome’s impact on human health. Initiatives such as the National Institutes of Health’s Human Microbiome Project (HMP), launched in 2007, aimed to push the field significantly forward by investing $215 million in research projects from 2007-2014. The program generated nearly 50,000 files of publicly available sequencing data which have been accessed by 75,000 users from 178 countries. Human microbiome research is already yielding health benefits, such as the use of fecal microbiome transplantation for curing Clostridium difficile infections in up to 90% of cases. Microbiome diagnostic tests for predicting which pregnant women are at risk for preterm labor (a leading cause of infant death) are under active development by The Mayo Clinic’s Center for Individualized Medicine and Whole Biome.

Why do we need a national microbiome initiative?

Microbiome research is a vastly expanding and productive field, but the pace of growth leaves huge potential for wasted resources through redundant research initiatives. A dozen federal agencies invested $922 million into microbiome research from 2012-2014 alone, with numerous individual initiatives at universities and private companies.

In October of 2015, a commentary in the prominent scientific journal, Science, put out a call for creating a coordinated, microbiome research effort to push the field forward. A high profile group of microbiome researchers and the newly formed Unified Microbiome Initiative Consortium argued that a greater understanding of “microbial functions or community dynamics” has the potential to “transform our understanding of the world and launch innovations in agriculture, energy, health, the environment, and more.” The commentary highlighted key research areas that can be effectively tackled with a united effort, including the following:

  • Better technology: Research must improve tools for predicting the function of the many uncharacterized genes uncovered, and a vast improvement must be made in understanding all of the chemical compounds produced in the biochemical pathways of microbes. One recent report found that only 2% of the data could be matched to known chemical compounds.
  • Jumping from gene to genome: Much of the current microbiome research focuses largely on the gene content of a given microbiome, but teasing out what genes are part of what organism will be essential to fully understand the whole “community function and dynamics.” This will require significant improvements in DNA sequencing and assembling technologies.
  • Integrating all the data: Studies often focus on different aspects of microbial communities, such as genes, expression of genes, proteins made, and chemicals produced. All of this data needs to be integrated along with potentially new high resolution imaging data to get a big picture view of the function of microbes in an ecosystem.
  • Translating observational research into action: Most research currently involves describing what microbes are present, i.e. in a healthy gut versus the gut of a person suffering from a disease. New methods are needed to move research in the direction of making changes in microbial communities to potentially generate disease treatments and environmental improvements. DNA editing technologies like CRISPR/Cas9 may play a role on this front.

What will NMI do?

NMI aims to pull together a number of federal agencies and stakeholders in order to coordinate research and set common goals. The project consists of three broad goals reported in the OSTP announcement:

  1. Supporting interdisciplinary research to answer fundamental questions about microbiomes in diverse ecosystems.
  2. Developing platform technologies that will generate insights and help share knowledge of microbiomes in diverse ecosystems and enhance access to microbiome data.
  3. Expanding the microbiome workforce through citizen science and educational opportunities.

NMI will commit $121 million from the 2016 and proposed 2017 Federal budgets into “interdisciplinary, multi-ecosystem research and tools development.” In a call to action from OSTP, numerous universities and private sector stakeholders committed over $400 million for additional microbiome research and development including projects aimed at the following:

  • Human and agricultural microbiomes (Bill and Melinda Gates Foundation, $100 million)
  • Microbiomes related to type 1 diabetes (JDRF, $10 million)
  • Technology development (Center for Microbiome Innovation, The University of California, San Diego, $12 million)
  • Microbiome data access for researchers, clinicians, and other public health professionals (One Codex)
  • Microbiome data and sample banks including underrepresented groups (The BioCollective, LLC, Health Ministries Network, $250,000)
  • Microbiome research and training programs under the Michigan Microbiome Project (The University of Michigan, Howard Hughes Medical Institute, Procter and Gamble, $3.5 million)
  • Microbiomes of health and disease, developing new therapies via the Center for Medicine and the Microbiome (University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center)

A complete list can be found in the OSTP announcement.

In order to be truly effective, however, the efforts to coordinate microbiome research will have to include the global scientific community. A commentary by several international microbiome researchers released in Nature in the fall of 2015 supports the efforts to unify the microbiome research community but goes on to argue that the microbiome research effort must be global in scope. It points out that at least eight separate human microbiome programs from various countries – including the US, Canada, the European Union, China and Japan – have generated huge amounts of data that are not easy to compare. International study standards, forums, and common tools would go a long way in ensuring that the public gets the most return on investment from every research dollar spent.

If NMI can lead the charge in setting the global microbiome research agenda, the world may benefit in a number of ways. The Science commentary notes that microbes have the potential to produce a nearly unlimited number of beneficial compounds, including biofuels and next-generation antibiotics. The study of ocean and soil microbes may paint a clearer picture of climate change. Agriculture may see improvements such as reducing the need for pesticides or rehabilitating soil depleted of nutrients. Human health may see potential interventions for conditions such as “asthma, diabetes, obesity, infectious diseases, psychiatric illnesses, and other afflictions.” Communication driven by NMI among key stakeholders, federal agencies, and the global community will be essential to delivering solutions for all of these areas in the next decade of microbiome research.

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Written by sciencepolicyforall

June 1, 2016 at 9:00 am

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