The Role of the Gut Microbiome in Health and Disease
The Role of the Gut Microbiome in Health and Disease
Traditional microbiology culture methods have proved largely unsuccessful in helping to determine the identity and function of the members of the gut microbial community, according to Fasano. "Less than one percent of bacteria that live with us in symbiosis has been cultured," he says. The identity of the gut microbiota he calls "the dark side of the moon."
"These organisms live so intimately with each other, each one making a substrate upon which others live. We are just learning how to emulate those conditions outside the gut," Danska says. She says a few laboratories are making progress culturing consortia of human gut commensals in specialized environments called chemostats.
The burgeoning field of metagenomics, a sequencing approach aimed at describing the genetic richness of whole microbial communities, has allowed researchers to probe the diversity of the body's microbiota much more deeply than traditional culture techniques. Classical microbiology is focused on questions such as strain-specific identification—whether a strain is pathogenic, its genetic contents, and any antibiotic resistance parameters. Microbiome analyses, on the other hand, can answer higher-order human health questions—namely, Danska says, "What is the functionality of the consortia of bacteria as a whole?"
Although metagenomics has proven a powerful tool in determining the diversity and metabolic potential of the microbiota, new approaches are needed to determine which microbes are active, which are damaged, and which may respond to a given compound. Some of them metabolize environmental toxicants including polycyclic aromatic hydrocarbons and metals such as arsenic, according to Lisa Chadwick, a program administrator in the National Institute of Environmental Health Sciences (NIEHS) Division of Extramural Research and Training.
Research suggests that short-term exposure to xenobiotics alters microbial physiology, community structure, and gene expression. For instance, studies with antibiotics have found immediate decreases in the stability and diversity of the gut microbiota with only partial recovery up to four years after treatment. And researchers at the University of Miami recently found that in mice exposed orally to polychlorinated biphenyls for two days, the overall abundance of bacteria in the gut was 2.2% lower than in unexposed mice, a statistically significant difference. However, physical exercise appeared to dampen changes to the gut microbiota.
These findings notwithstanding, the question of which microorganisms, genes, and pathways are involved in xenobiotic metabolism remains largely unanswered. And the impacts on the microbiota of the thousands of different environmental agents to which the body is exposed each day remain largely unstudied.
"As environmental health scientists, we think a lot about the environment and the role it plays in the developmental origins of disease. Early-life exposures may also change the trajectory of how the microbiome develops and contribute to the development of exposure-related diseases later in life," says Chadwick. "Now that we are starting to get to know the basic biology of the microbiome, we can start applying that research to environmental health." Chadwick says the NIEHS will award approximately $2 million in grants in fall 2013 to fund microbiome research projects.
Unraveling the function of the microbiota in disease may offer potential clues to treatment. Researchers on the leading edge of microbial therapy are experimenting with fecal transplantation to help restore healthy microbial communities in patients with inflammatory bowel diseases. Others are hopeful that microbiome studies will lead to therapies for a variety of diseases—immunological, metabolic, and neurological—that have been linked to gut bacteria.
"From my perspective, it's going to be easier to make and sustain changes to the [microbiota] of individuals than to come up with drugs to alter immune pathways," says Danska. "I believe that within a handful of years, in countries with high-quality medical care, we will start to see routine administration of well-defined combinations of bacteria to children to prevent autoimmune-mediated diseases."
However, the personalized nature of such treatments may prove an obstacle that investigators will need to overcome. Mazmanian says, "The same therapy may not work for all people. Specific formulations may have to match the genetics of the patient."
Assessing the Influence of Environmental Agents
Traditional microbiology culture methods have proved largely unsuccessful in helping to determine the identity and function of the members of the gut microbial community, according to Fasano. "Less than one percent of bacteria that live with us in symbiosis has been cultured," he says. The identity of the gut microbiota he calls "the dark side of the moon."
"These organisms live so intimately with each other, each one making a substrate upon which others live. We are just learning how to emulate those conditions outside the gut," Danska says. She says a few laboratories are making progress culturing consortia of human gut commensals in specialized environments called chemostats.
The burgeoning field of metagenomics, a sequencing approach aimed at describing the genetic richness of whole microbial communities, has allowed researchers to probe the diversity of the body's microbiota much more deeply than traditional culture techniques. Classical microbiology is focused on questions such as strain-specific identification—whether a strain is pathogenic, its genetic contents, and any antibiotic resistance parameters. Microbiome analyses, on the other hand, can answer higher-order human health questions—namely, Danska says, "What is the functionality of the consortia of bacteria as a whole?"
Although metagenomics has proven a powerful tool in determining the diversity and metabolic potential of the microbiota, new approaches are needed to determine which microbes are active, which are damaged, and which may respond to a given compound. Some of them metabolize environmental toxicants including polycyclic aromatic hydrocarbons and metals such as arsenic, according to Lisa Chadwick, a program administrator in the National Institute of Environmental Health Sciences (NIEHS) Division of Extramural Research and Training.
Research suggests that short-term exposure to xenobiotics alters microbial physiology, community structure, and gene expression. For instance, studies with antibiotics have found immediate decreases in the stability and diversity of the gut microbiota with only partial recovery up to four years after treatment. And researchers at the University of Miami recently found that in mice exposed orally to polychlorinated biphenyls for two days, the overall abundance of bacteria in the gut was 2.2% lower than in unexposed mice, a statistically significant difference. However, physical exercise appeared to dampen changes to the gut microbiota.
These findings notwithstanding, the question of which microorganisms, genes, and pathways are involved in xenobiotic metabolism remains largely unanswered. And the impacts on the microbiota of the thousands of different environmental agents to which the body is exposed each day remain largely unstudied.
"As environmental health scientists, we think a lot about the environment and the role it plays in the developmental origins of disease. Early-life exposures may also change the trajectory of how the microbiome develops and contribute to the development of exposure-related diseases later in life," says Chadwick. "Now that we are starting to get to know the basic biology of the microbiome, we can start applying that research to environmental health." Chadwick says the NIEHS will award approximately $2 million in grants in fall 2013 to fund microbiome research projects.
Unraveling the function of the microbiota in disease may offer potential clues to treatment. Researchers on the leading edge of microbial therapy are experimenting with fecal transplantation to help restore healthy microbial communities in patients with inflammatory bowel diseases. Others are hopeful that microbiome studies will lead to therapies for a variety of diseases—immunological, metabolic, and neurological—that have been linked to gut bacteria.
"From my perspective, it's going to be easier to make and sustain changes to the [microbiota] of individuals than to come up with drugs to alter immune pathways," says Danska. "I believe that within a handful of years, in countries with high-quality medical care, we will start to see routine administration of well-defined combinations of bacteria to children to prevent autoimmune-mediated diseases."
However, the personalized nature of such treatments may prove an obstacle that investigators will need to overcome. Mazmanian says, "The same therapy may not work for all people. Specific formulations may have to match the genetics of the patient."
