Duke researchers discover link between microbes and genes

<p>New treatments for inflammatory bowel disease and diabetes may be possible after&nbsp;a study including Duke researchers found that the&nbsp;presence of microbes reduces the activity of a transcription factor that&nbsp;plays a role in those diseases.</p>

New treatments for inflammatory bowel disease and diabetes may be possible after a study including Duke researchers found that the presence of microbes reduces the activity of a transcription factor that plays a role in those diseases.

The millions of tiny microbes within a human body—collectively termed the body's microbiome—could affect how genes are expressed, according to a new study by Duke researchers.

In the study published in the journal Genome Research, scientists determined that the presence of microbes reduces the activity of a transcription factor and protein known as HNF4A. This factor plays a role in inflammatory bowel diseases and diabetes, so the discovery may help lead to the development of new treatments.

“Our microbiome is known to influence many different aspects of our health, and they achieve this in part by affecting the activity of our genes,” said senior author John Rawls, associate professor of molecular genetics and microbiology in the Medical School. “Here, we discovered a new mechanism by which the microbiome turns host genes on and off in the intestine.”

Lead author and University of North Carolina at Chapel Hill graduate student James Davison noted that the complexity of the microbiome can make it a difficult area to research. The community of cells inside the body's intestine—including bacteria, fungi, viruses and human intestinal cells—are all communicating with one another in many different ways, he explained. Diet can also affect the signaling between these cells.

“Specific mechanisms that mediate microbial contributions to human health are difficult to identify due to ecological complexity of the intestinal lumen,” Davison said.

While this experiment did not isolate a specific mechanism, it did show a previously unknown interaction between the microbiome and the transcription factor HNF4A. Rawls explained that transcription factors—which are proteins “that bind to DNA in specific locations to modify the activity of neighboring genes”—are one way in which humans and other animals control the expression of their genes.

HNF4A is a member of an ancient class of transcription factors known as nuclear receptors and originated in a common ancestor of humans and sponges, he noted.

Rawls added that this experiment—performed on both zebrafish and mice—suggests that the interaction between the microbiome and HNF4A has been present since “the earliest stages of vertebrate evolution.”

The study's findings could benefit the millions of people who suffer from inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Davison noted that a change in HNF4A activity had already been linked to these diseases.

“Inflammatory bowel diseases are associated with dysregulation of genes in the intestine,” Davison said. “We may be able to partly correct this dysregulation by targeting HNF4A in a drug or dietary therapy.”

However, the development of a treatment will require more thorough investigation into the specific interactions between the microbiome and HNF4A. Both researchers noted that pinpointing the mechanism by which microbes are able to suppress HNF4A is essential in pursuing this line of research.

In addition, Rawls expressed interest in identifying which microbes contribute to this HNF4A reduction.

“This work reveals an ancient mechanism of communication between microbes and their vertebrate hosts,” Rawls said. “It’s striking then that this ancient interaction also appears to be relevant for modern-day human disease such as the inflammatory bowel diseases.”

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