Building New Knowledge
Steve Rappaport, a professor of environmental health sciences at the University of California, Berkeley, says the environ-mental health community is now beginning to embrace a new concept that goes beyond the microbiome. This new concept is the "exposome," which the National Institute for Occupational Safety and Health defines as the measure of all of an individual's exposures over his or her lifetime and how those exposures affect disease risk. Rappaport says the environmental exposures that affect human health may include "all kinds of endogenous processes that have so far escaped our interest in finding the environmental causes of disease"—including the microbiome and inflammatory processes.
The concept of the exposome blurs the distinction between exposure and response. "For years we talked about biomarkers, and we differentiated between biomarkers of exposure and biomarkers of response," Rappaport says. "But when you really start drilling down into that concept of a biomarker, it can become difficult to make that differentiation."
A recent example of this blurriness is a discovery by a group led by Stanley Hazen of the Cleveland Clinic's Department of Cell Biology. The researchers reported identifying trimethyl-amine N-oxide (TMAO) as a biomarker that is highly predictive of cardio-vascular disease in Americans, and they provided evidence the intestinal microbiome plays a role in generating TMAO. The process begins with choline, an essential micronutrient, which intestinal bacterial transform catabolically to trimethylamine (TMA). TMA can be absorbed into the blood, where it is transported to the liver and metabolized to produce TMAO. But it is still unclear whether TMAO is a biomarker of the presence of choline, a particular intestinal bacterium, metabolism of TMA in the liver, factors related to arterial inflammation, or some combination of all of these, Rappaport says.
From a regulatory perspective, Rita Schoeny, senior science advisor for the EPA Office of Water, says revelations at the April NAS conference about the potential role of the microbiomes in disease risk raise many questions. For instance, EPA regulations for arsenic, and to some extent for mercury, are based on what scientists understand to be "a lovely progression of reduction and methylation with more reduction and methylation"—none of which, she says, considers microbial metabolism. Schoeny says the EPA Office of Water regulates microbes as something to be avoided, particularly in drinking water, under the assumption that the "only good bug is a nonexistent bug"; the microbiome is currently not on the agency's radar in terms of policy making.
Vincent Cogliano, director of the EPA's Integrated Risk Information System, told participants at the April meeting he is concerned about the absence of microbiome information in the interpretation of toxicity testing results. "Regulatory agencies are putting a lot of effort into understanding the sequence of mechanistic events that lead to disease. It looks like we have been ignoring a big number of these events that could be there," he said. He likened the current approach to trying to write a novel without any prepositions. "You can put some coherent thoughts together," he said, "but you cannot tell a story that is very complex or very interesting."
How might our growing awareness of microbiomes inform public health policy? Bruce Fowler, assistant director for science in the Division of Toxicology and Environmental Medicine at the Agency for Toxic Substances and Disease Registry, says it comes down to translational risk assessment. "We recognize that there are individuals within the population who are especially sensitive to chemicals as a result of age, life stage, diet, nutrition, what have you," Fowler said at the April meeting. "I think the microbiome just quite simply hasn't been plugged into this, and I think it should be."
Lisa Helbling Chadwick, the NIEHS liaison for the Human Microbiome Project, says the institute is increasing its focus on the impact of microbiomes on toxicology. "One thing we are really interested in at NIEHS is understanding how individuals respond differently to exposures, what makes one person more susceptible to adverse health outcomes from an exposure than another," she says. "Genetics only partially explains this." Birnbaum adds, "We recognize the enormous implications of the growing awareness of interactions between chemical exposures and the microbiome, and we have begun exploring these issues."
Environ Health Perspect. 2011;119(8):a340-a346. © 2011 National Institute of Environmental Health Sciences
Cite this: A Study in Balance: How Microbiomes are Changing the Shape of Environmental Health - Medscape - Aug 01, 2011.