Microbes seen controlling action of host's genes

All animals-from sea sponges to modern-day humans-evolved in a world already teeming with microbes. These single-celled microorganisms now cover practically every surface of our bodies and are as much a part of our biology as our own tissues and organs. They educate our immune system, regulate our metabolism, and as it turns out, even influence our behavior. 

Duke researchers have shown that microbes can control the actions of their animal hosts by manipulating the molecular machinery of animal cells, triggering patterns of gene expression that consequently contribute to health and disease. The work, which was conducted in zebrafish and mice, could have implications for human inflammatory bowel diseases like Crohn's disease and ulcerative colitis. The findings appear in the journal Genome Research.

"Our results suggest that ancient parts of our genome and ancient interactions with our microbes are relevant to modern-day human diseases," said John F. Rawls, Ph.D., senior author of the study and associate professor of molecular genetics and microbiology at Duke University School of Medicine.

A graduate student in the Rawls lab, James M. Davison, compared genetic regions linked with gene regulation in two sets of mice: one that was germ-free and one that had their bellies loaded with microbes. He discovered that a large number of enhancers behaved differently in the presence of microbes. When he looked closer, he found that some of these elements bound a protein called Hnf4a, an ancient animal transcription factor that had previously been implicated in a number of human diseases, including inflammatory bowel diseases, obesity and diabetes.