Environmental Factor, December 2010, National Institute of Environmental Health Sciences
NIEHS hosts workshop on gut microbiome
By Eddy Ball
With its latest state-of-the-science workshop, the NIEHS Superfund Research Program (SRP) took a proactive step forward Nov. 17-18 to promote an exciting new area of research in environmental health science. The purpose of the meeting was to assess existing research and explore new directions in investigating the role of the human digestive tract - or gut - ecology in health and disease, with a focus on its impact on host susceptibility and response to a wide range xenobiotic exposures.
The interdisciplinary group of scientists gathered at NIEHS to review the growing body of literature on the microbiome, the microbial communities inhabiting the human body. The scientists were particularly interested in how microbes interact with the host and environmental exposures to impair optimal health, as well as initiate or promote diseases, including cancer, in the digestive tract and elsewhere in the body.
Although the gastroenterological community is becoming more keenly aware of the power of the trillions of microbes that inhabit the human gut, the ecology of the microbiome and its effects on extraintestinal disease and host gene expression remain largely uncharted - underscoring how instrumental this workshop may prove to be in advancing scientific awareness of the microbiome's role in health and disease.
In his welcome to attendees at the meeting, jointly sponsored by NIEHS and Michigan State University (MSU) (http://iit.msu.edu/) , SRP Director Bill Suk, Ph.D., linked research on the host-microbiome-xenobiotic interaction to SRP program mandates. "If we're going to be able to assess human risk and exposure leading to disease, we have to be able to understand all of the factors and all of the cofactors associated with the host's processes. Obviously, the microbiome is a significant part of that paradigm."
The workshop began with a talk by a pioneer and leading authority in the investigation of the microbiome. Plenary presenter Jeffrey Gordon, M.D. (http://gordonlab.wustl.edu/) , is the director of the Center for Genome Sciences at the Washington University in St. Louis School of Medicine.
The humorous subtitle of Gordon's talk - "Dining in with trillions of fascinating friends" - set the tone for discussions of the magnitude and complexity of the landscape of the microbiome. As he explained, human intestinal microbes exceed the number of host somatic and germ cells by 10-fold, and their aggregate genome is more than 100-fold greater in size than the human genome.
Gordon surveyed research in the field, as well as his lab's studies on the effects of fecal transplantation of microbiome samples from humans in sterile mice. In his studies, Gordon compares human samples from the United States, Malawi, and South America. Gordon is investigating the colonization patterns associated with diseases, the gene-microbiome interactions, and treatments to restore healthy microbial balance.
Following Gordon's presentation, the talks and breakout discussions that structured the workshop focused on three key questions:
- What is the state of current knowledge about the composition of the gut microbiome, and what leading edge technologies and approaches are being used to advance the science?
- How does the gut microbiome influence disease and health of the host?
- How do interactions between xenobiotics and the gut microbiome affect toxic response?
The meeting concluded with summations by breakout group facilitators and rapporteurs that understandably produced more questions than confident answers. According to organizers, workshop conclusions will be published in an upcoming paper, possibly as a commentary in the NIEHS journal Environmental Health Perspectives.
Despite the many unanswered questions, by the end of the workshop one thing was clear - the impact of the microbiome on human health cannot be ignored or marginalized in the promotion of public health and pursuit of effective strategies for the prevention of disease.
A diverse and impressive group of speakers
Commenting afterwards about the success of the workshop, SRP Program Analyst Beth Anderson described organizer Norbert Kaminski, Ph.D. (http://iit.msu.edu/faculty/kaminski.html) , as a "visionary [who was] responsible for the design and content of the meeting." Kaminski, who is director of the Center for Integrative Toxicology at MSU, invited leading authorities on the microbiome whose interests and approaches reflect the breadth of interdisciplinary work in the field:
- David Relman, M.D., assistant professor in the Departments of Medicine and Microbiology and Immunology at the Stanford University School of Medicine - "Stability and responsiveness of the human gut microbiota"
- Vincent Young, M.D., Ph.D., associate professor in the Departments of Internal Medicine and Microbiology and Immunology at the University of Michigan - "Structure and function of the indigenous gut microbiota"
- Gary B. Huffnagle, Ph.D., professor in the Departments of Internal Medicine, and Microbiology and Immunology, Pulmonary Division, at the University of Michigan - "Regulation of mucosal immunity by the indigenous microbiota"
- Robert L. Hettich, Ph.D., senior research staff scientist in the Chemical Sciences Division at the Oak Ridge National Laboratory - "Integrating metagenomics with metaproteomics for comparing the molecular activities of the human distal gut microbiome in healthy vs. Crohn´s diseased individuals"
- Patricia E. Ganey, Ph.D., professor in the Department of Pharmacology and Toxicology at Michigan State University - "Microbial products enhance xenobiotic-induced liver injury"
- Arlin B. Rogers, D.V.M., Ph.D., assistant professor of molecular therapeutics at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center - "The influence of gut microbes on extraintestinal cancers"