Tens of trillions of bacteria, viruses, parasites and fungi live in and on the human body. Known collectively as the microbiome, this community of microbes has profound effects on our health, influencing the risk of developing conditions ranging from obesity to inflammatory bowel disease to schizophrenia.
A longtime leader in microbiome research, Washington University School of Medicine in St. Louis plans to build a research center dedicated to studying the microbiome in health and disease. The center – funded with an $8 million grant from the National Institutes of Health (NIH), along with $2.8 million from the School of Medicine – will provide a sterile place to breed and house mice with no microbiomes of their own. By introducing carefully selected microbes into such mice and studying the effects, researchers from across the School of Medicine will be able to investigate the role of the microbiome in human growth and development, behavior, metabolism, inflammation, infectious disease immunity, neurodevelopment, neurodegeneration and other conditions.
“Jeffrey Gordon, MD – one of our most well-respected investigators and an internationally recognized leader in microbiome research – pioneered the use of germ-free mice to study the microbiome, but we’ve never had a hub for doing this kind of research,” said Jennifer K. Lodge, vice chancellor for research at Washington University, who is spearheading the project. “He has been called the father of the microbiome because his discoveries on the importance of the gut microbiome revolutionized our understanding of human biology. More than 50 investigators at the School of Medicine have told me that their research would benefit from a facility to study the microbiome. I am excited that we will be able to provide such a facility to our investigators.”
The center will be known as the Gnotobiotic Research, Education and Transgenic (GREaT) center, and it will be constructed within an existing building on the Medical Campus. The term “gnotobiotic” refers to animals whose microbiomes are precisely known and controlled. Germ-free mice, which have no microbiomes at all, are one kind of gnotobiotic mice. The ability to control the microbiome will allow researchers to investigate how microbes interact with each other and human cells to influence human physiology.
“This new center will enable Washington University investigators to conduct a wide array of critical experiments, including analyzing the physiologic effects of individual microbes, human or mouse microbial communities, and metabolites,” said Megan Baldridge, MD, PhD, an assistant professor of medicine and of molecular microbiology. “The use of germ-free mice permits highly controlled studies of the microbiome that simply can’t be achieved through any other means.”
The center – which was designed by an advisory committee comprised of Phillip I. Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics and director of the Division of Pediatric Gastroenterology, Hepatology and Nutrition; Nicholas O. Davidson, MD, DSc, the John E. and Adaline Simon Professor of Medicine and director of the Division of Gastroenterology; and Thaddeus Stappenbeck, MD, PhD, the Conan Professor of Laboratory and Genomic Medicine and co-director of the Division of Laboratory and Genomic Medicine – will enhance research into a variety of conditions. For example:
- Some successful treatments for type 2 diabetes seem to work by changing the physiology of the gut microbiome. Researchers could use gnotobiotic mice to identify the microbes – and their metabolites – that are altered by treatment. Identifying these factors would enhance understanding of type 2 diabetes and its treatment, and could lead to ways to refine and improve therapies.
- The microbiome has been linked to neuropsychiatric conditions such as depression, autism and schizophrenia, possibly because gut microbes can produce metabolites that act on the nervous system. A gnotobiotic research facility would allow researchers to untangle the effects of the microbiome and neuroactive metabolites on neuropsychiatric disorders.
- The microbiome influences how well the body’s immune system fights infection, repairs wounds and controls cancer. It also plays a role in inflammatory and autoimmune diseases such as atherosclerosis, inflammatory bowel disease and type 1 diabetes. By using genetically modified mice to model different aspects of the immune system, researchers can tease out the relationship between the microbiome and specific human immune genes and proteins in a variety of conditions. Such data could lead to new preventive and therapeutic strategies.