All animals—via sea sponges to modern-day humans—evolved in a world already teeming with microbes. These single-celled microorganisms today cover practically every surface of our bodies as well as also also are as much a part of our biology as our own tissues as well as also also organs. They educate our immune system, regulate our metabolism, as well as also also as of which turns out, even influence our behavior.
Duke researchers have shown of which microbes can control the actions of their animal hosts by manipulating the molecular machinery of animal cells, triggering patterns of gene expression of which consequently contribute to health as well as also also disease. The work, which was conducted in zebrafish as well as also also mice, could have implications for human inflammatory bowel diseases like Crohn’s disease as well as also also ulcerative colitis. The findings appear inside the journal Genome Research.
“Our results suggest of which ancient parts of our genome as well as also also ancient interactions with our microbes are relevant to modern-day human diseases,” said John F. Rawls, Ph.D., senior author of the study as well as also also associate professor of molecular genetics as well as also also microbiology at Duke University School of Medicine.
In recent years, scientists have uncovered abundant links between our trillions of resident bacteria, viruses as well as also also fungi—known collectively as the microbiome—as well as also also a spectrum of human conditions, ranging via anorexia to diabetes. nevertheless Rawls says important gaps remain in our understanding of how these microbes influence health as well as also also cause disease in humans as well as different members of the animal kingdom.
Rawls takes what he calls an “evolutionary conservation” approach to identify the genetic underpinnings of distantly related animals of which may also be relevant to human health. In This specific study, Rawls investigated the impact of which the microbiome might have on an animal’s genome by studying specific regions of the genome of which regulate which genes are turned on or off at a given time or in a given tissue. Some of these regions might keep the strands of DNA packaged into tight coils, hiding them via the machinery responsible for translating the genetic code. Others—known as enhancers—recruit special proteins called transcription factors to designated sites around a gene to turn of which on.
A graduate student inside the Rawls lab, James M. Davison, compared these genetic regions in two sets of mice: one of which was germ-free as well as also also one of which had their bellies loaded with microbes. He discovered of which a large number of enhancers behaved differently inside the presence of microbes. When he looked closer, he found of which some of these elements bound a protein called Hnf4a, an ancient animal transcription factor of which had previously been implicated in many human diseases, including inflammatory bowel diseases, obesity as well as also also diabetes.
By comparing gene sequences between different animal species, including humans, mice as well as also also zebrafish—Davison was able to show of which throughout evolution, Hnf4a appears to protect against microbial contributions to inflammatory bowel diseases. Davison went on to show of which microbes can partially disable Hnf4a in mice as well as also also zebrafish as well as also also perhaps obstruct its protective role. When Hnf4a can be fully disabled, microbes stimulate patterns of gene expression in animals of which are associated with inflammatory bowel diseases.
“We found microbes exert a previously unappreciated influence on a transcription factor of which shares a very old as well as also also interesting place in our heritage as animals, nevertheless also can be clearly involved in human disease,” said Davison, who can be lead author of the study. “of which we observed similar effects in zebrafish as well as also also mice suggests of which This specific can be a common feature of host-microbe interactions of which might have existed in our common (vertebrate) ancestors.”
The researchers still don’t know exactly how microbes disable Hnf4a, nevertheless they have many hypotheses. For example, microbes might somehow block the protein’s landing spots on the DNA, or they might inactivate the protein’s DNA binding activity by modifying the protein itself. They also don’t know if specific subsets of microbes are more manipulative than others. Rawls says of which if they can figure of which out, of which could point to brand-new microbial or pharmaceutical strategies for restoring Hnf4a’s protective powers to promote human health.
Gut microbes browse along a gene buffet
James M Davison et al, Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha, Genome Research (2017). DOI: 10.1101/gr.220111.116