29 January, 2019
“Gordon and his team were the first to demonstrate the importance of the gut microbiome in regulating animal physiology,” the citation continues. “Following this fundamental discovery, it has been shown by many groups around the world that the gut microbiome plays a central role in health and in disease, including obesity, diabetes and inflammatory bowel disease, and perhaps will have great implications on the pathogenesis of neurological disorders and response to drug therapy.”
Gordon’s work has ushered in a brand new area of basic research in biomedicine exploring the role of microbes in the body’s healthy functioning, and has enabled new research directions in the study of multiple conditions, as well as the search for novel treatments.
Gordon discovered, for instance, that gut flora may contribute to the onset of obesity. And he was also able to show that the long-term effects of childhood malnutrition, like impaired brain and immune system development, are determined not only by diet but also by the assembly or otherwise of a healthy microbiome.
Further ahead, his work may herald a new era of microbiome-based therapies. As the committee remarks, “fecal microbiota transplantation can be beneficial for the treatment of some disease conditions, including types of colitis. As the precise molecular mechanisms of the role of bacteria in our physiology are being discovered, this will have great promise for the development of targeted therapeutics for diverse human diseases.”
A human-microbe “symbiosis” essential to health
Science has long known that the human body teems with microbial species that colonize every available surface. But what it failed to suspect was how important these communities are. In fact, Gordon and his group only got interested in gut flora as part of their research on intestinal development. While exploring the chemical signals cells exchange as they go about building the gut, Gordon found that the microbes that live there converse constantly with our cells, and perform services that they rely on. One such service would be digesting nutrients that the human body cannot metabolize.
This discovery that microbes and their human hosts exist in a symbiotic state essential to their mutual survival was a major paradigm shift. The new laureate explained it thus after hearing of the award: “We cannot live or function alone; there is this ongoing collaboration between ourselves and the tens and tens of trillions of microbes that inhabit our bodies.”
“People should step back and take a more expanded view of what we truly are; this splendid collection of microbial and human cellular and genetic parts,” Gordon enthuses. “There are over a hundred-fold more microbial genes than human genes in our bodies, and in this respect we are more bacterial than human, but we benefit from one and other’s company. The question is the degree to which our biological features are an expression of our microbial contributions.”
Gordon declares himself “captivated” by the idea that hundreds of millions of years ago a much simpler organism had to decide whether it had enough genes to metabolize the nutrients it needed, or whether it should coopt those of other life forms, forging a symbiotic relationship that has lasted to this day. “Most people’s view of microbes is in the context of war and conflict, rather than cooperation and collaboration, but what our research has revealed is that microbes can be our friends.”
The role of the microbiome in obesity and malnutrition
To elucidate the role of gut microbes, Gordon and his team used mice reared under sterile conditions, so they harbored no microbes of their own. They then colonized them with known members of the gut microbial community to observe how they reacted to particular nutrients. This kind of research has produced firm evidence that microorganisms are causally related to diseases like obesity, as well as having a role to play in the treatment of malnutrition.
As Gordon explains it, “our research journey has focused on what is normal in human microbial communities, and whether deviations from normal are associated with disease.”
The new field of microbiome research is right now a hive of activity, but Gordon cautions that “we need to keep sight all we still have to learn.” It may be tempting to think that there are “fattening” and “slimming” microbes, but it will never be that simple: the effect of each microbiome is personal and specific, because “the important thing is the interaction” between the microbes and the host’s cells.
Reduced microbial diversity in the West
One fact that emerges is that the enormous diversity of the human microbiome is being eroded in Western societies: “We looked at the microbiomes of people living in different parts of the world, and saw that in Westernized societies there has been a loss of the diversity of these microbial communities, and that is not good. It is a reflection of our lifestyles and our diets, a reflection perhaps of the things that we consume, including our promiscuous use of antibiotics.”
Looking to the future, Gordon is hopeful that “we will learn how to feed ourselves in more healthful ways, improving the content of staple foods to the benefit of the consumer’s microbiome, and making better decisions on how food should be processed to maintain the active ingredients and by this means improve the nutritional status of different populations.”
Jeffrey I. Gordon earned a degree in medicine from the University of Chicago in 1973. He went on to do his clinical training in internal medicine and gastroenterology, completing a post-doctoral fellowship at the National Institutes of Health (NIH). In 1981, he joined the faculty at Washington University in St. Louis (Missouri, United States), where he remains to this day.
A varied teaching and research career in medicine, biological chemistry and molecular biophysics took him through the ranks of academia to the two positions that he holds today, as Dr. Robert J. Glaser Distinguished University Professor and Director of the Edison Family Center for Genome Sciences and Systems Biology. In this time, he also served as Chair of the Executive Council of the Division of Biology and Biomedical Sciences, overseeing all graduate education in the biological sciences.
The author of more than 500 papers in international journals and with 24 patents to his name, he has been thesis mentor to 63 PhD and MD/PhD students and research mentor to 68 post-doctoral fellows. He is a member of the editorial boards of Cell Metabolism, Cell Host and Microbe, and Science Translational Medicine. The gut bacterium Parabacteroides gordonii, isolated in 2009, was named in his honor.