Like many people, I have gone through life without paying much attention to my gut –- except, that is, for the times my stomach gave unmistakable indications that it was upset. Most of the time, what was happening inside said stomach remained unknown. On the whole, it was out of sight, out of mind. But now, the cover story of the new Penn Medicine magazine provides an illuminating look at the human gut microbiome. For example, we learn some staggering numbers in “Microbiomics: The Next Big Thing?”
As Lisa J. Bain, the writer, points out, researchers with the National Institutes of Health’s (NIH) Human Microbiome Project have determined that the human gut microbiome alone is home to 100 trillion bacteria –- ten times the number of cells in the human body. In addition, it also contains around 8 million protein-coding genes, 360 times as many as in the human genome. My gut, it seems, is more crowded than I ever would have suspected!
And there are viruses as well. Frederic Bushman, PhD, a professor of microbiology featured in the Penn Medicine article, was senior author of a notable study published in Genome Research in 2011. Describing what his team found, Bushman cited “the vast viral populations that live in the human gut.” The study provided more evidence that the interactions between viruses, bacteria, and the human host are likely to have significant consequences for human health and disease. Bushman had a rather elegant metaphor: “Our bodies are like coral reefs, inhabited by many diverse creatures interacting with each other and with us.”
New Tools = New Knowledge and New Questions
Knowledge of the microbiome has increased very rapidly, and scientists at Penn have contributed. Researchers have been able to map the microbiome because of the advanced technology for gene sequencing that was used in the Human Genome Project. Bushman has been one of the leaders in the effort to profile complex microbial communities and map the evolutionary relationships of diverse species of commensal bacteria. Scientists have learned that a change in the composition of those bacteria –- a disturbance in the ecosystem -– can be associated with a wide range of human diseases, including inflammatory bowel disease, asthma, arthritis, and multiple sclerosis. In the Penn Medicine article, Bain notes that one of the fundamental questions scientists are grappling with is whether those changes in bacterial diversity are a consequence of the disease. Or, on the other hand, do the bacteria have a role in the development of the diseases?
Following the Human Genome Project, the NIH launched a similarly ambitious project, the Human Microbiome Project (HMP), in 2007. The HMP’s goal is to map the collective genomes of the human microbiota. Bushman is working with two Penn professors of gastroenterology –- Gary Wu, MD, and James Lewis, MD, MSCE -– on one of 15 HMP demonstration projects. They are examining how diet influences the gut microbiome in people with Crohn’s disease, a particularly insidious type of intestinal bowel disease.
Because of its complexity, microbiomics tends to draw from many disciplines. Penn, with its many departments, schools, and multidisciplinary centers and institutes, is an ideal place for such a study. Ronald Collman, MD, professor of medicine and co-director of the Penn Center for AIDS Research, became interested in the microbiome as a means of better understanding how HIV triggers lung complications in infected people. As Collman puts it, “This is a really unique place in that we have great interactions and collaborations between clinical/translational microbiologists like me, and more basic molecular/computational microbiologists like Rick Bushman. It’s a very synergistic collaboration.”
Read more about the varied and often collaborative approaches to studying the human microbiome at http://www.uphs.upenn.edu/news/publications/PENNMedicine/files/spring2014_microbiomics.pdf