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Human microbiome meeting highlights research progress in a field already beginning to matter
By Steven Benowitz
Associate Director of Communications, Extramural Research Program
To the organizers - which included scientists from the University of Maryland School of Medicine in Baltimore, the National Institutes of Health (NIH) and elsewhere - the meeting was an important opportunity to evaluate the state of the science for this emerging field, and give feedback on gaps, needs and challenges.
Participants talked about how to study the human microbiome, the need for more uniform rules and standards on collecting samples, and how to best to analyze data. Presentations explored how lifestyle, age and drugs affect the microbiome, and provided evidence for its potential role in obesity, cancer and behavior.
The meeting also explored research options to build on the Human Microbiome Project (HMP). This five-year project, organized under the NIH Common Fund, culminated in 2012 with the publication of the first map of the normal microbial community make-up of people - as well as the genetic potential of these microbial communities - and established a valuable reference database.
Organizers convened the meeting, in part, because so many of the 27 institutes and centers at NIH either have microbiome research programs in place or are interested in exploring microbiome-themed research, said Lita Proctor, Ph.D., HMP coordinator at the National Human Genome Research Institute (NHGRI). "Some institutes are just getting started and trying to figure out where microbiome research fits into their individual research portfolios. This meeting was intended to provide an overview of this field for these institutes," she said.
Presenters covered a wide range of microbiome-related science, including basic biology and the diversity of the microbiome; tools and approaches for study of the microbiome; and the potential direct applications of the microbiome to human health, including its role in immunity, asthma and heart disease. This diversity was reflected in the titles of some of the talks such as, "Eczema, Immunity and the Skin Microbiome," "The Lung Microbiome: Challenging Old Paradigms about Microbes and the Host Respiratory Tract," and "Diet, Childhood Nutrition and the Microbiome."
In one talk, Maria Dominguez-Bello, Ph.D., of New York University, discussed, "The Modern vs. Ancestral Microbiome." Scientists have suggested that human microbiomes may be greatly affected by lifestyle and environment. The majority of human microbiome studies have focused on Western populations, causing some scientists to wonder if this research represents the so-called "natural" microbiome. To find out, Dr. Dominguez-Bello and her research team ventured to remote areas of South America, including the Amazon basin, to study the microbiomes of indigenous peoples such as the Yanomamo Indians. There, they uncovered surprising differences in microbial diversity, and are now evaluating the potential impact of these differences in the microbiomes between the Yanomami and Westernized populations.
Another presenter explored the role of microbes in inflammation, and as a factor in cancer development. Christian Jobin, Ph.D., from the University of Florida School of Medicine, described evidence showing that certain microbial cells not only caused inflammation in host cells, but can cause direct DNA damage to the host genes, demonstrating two mechanisms for a microbial role in the progression of cancer.
Ruth Ley, Ph.D, from Cornell University in Ithaca, N.Y., is studying how the gut microbiome affects the host. The microbiome changes over a lifetime, and rapidly shifts in childhood and beyond in response to diet, illness, medical treatments - particularly antibiotics - and more. She called for more studies to unravel which human genes interact with microbiota and how that interaction occurs. She is studying twins to develop an understanding of the genetic basis for how the microbiome affects metabolism. Dr. Ley would also like to better understand the role of the microbiome in influencing behavior and perhaps in fertility and longevity.
Several speakers described translating human microbiome research into clinical treatments. Elaine Petrof, Ph.D., of Queen's University in Kingston, Ontario, Canada, discussed how microbial ecosystems may be useful in treating drug-resistant Clostridium difficile infections. Alexander Khoruts, M.D., from the University of Minnesota in Minneapolis, described the great promise of fecal microbiome transplants to help people with potentially life-threatening intestinal disease. U.S. Food and Drug Administration Chief Scientist Jesse Goodman, M.D., M.P.H., provided the FDA perspective on potential applications from the microbiome.
Many challenges remainSpeaker after speaker stressed the need for more research. As one example of the need for basic research, a second phase of HMP is set to begin with new funding ($15 million over three years for two or three research teams) from the NIH Common Fund for FY13 to FY15, along with support from other NIH institutes and centers. This new phase will explore the biology of the microbiome in relation to its role in health and disease.
"After the first HMP phase, the question for us was, what biological properties of the microbiome do we need to measure in order to understand its relationship to human health?" Dr. Proctor said. "That's a huge undertaking, so we approached this question in a more limited fashion. We're hoping these new grants will help establish new microbiome research models and create a community resource for evaluating which biological properties will be the most informative when studying the role of the microbiome in health and in disease."
Looking ahead, Rob Knight, Ph.D., at the University of Colorado in Boulder, listed many questions and challenges for the microbiome research field, including reducing the cost of microbiome sequencing for use in the clinic, moving from correlation to causation in research studies, translating findings in animal models to humans and the regulation of microbiome-based therapies.
"There is such a diversity of ways in which the microbiome is being linked to different health conditions that span the interests of many NIH institutes and centers," said Dr. Knight. "We're seeing impressive advances in knowledge and technology that are allowing us to go from basic biological knowledge to potential clinical relevance on a much shorter timescale than has been possible in other fields."