Changes in the diet affect epigenetics via the microbiota

November 23, 2016
Nacho Vivas, lab manager at the Rey Lab in the Bacteriology Department at the University of Wisconsin-Madison, checks on a group of germ-free mice inside a sterile lab environment on June 22, 2015. Credit: Bryce Richter/UW-Madison

You are what you eat, the old saying goes, but why is that so? Researchers have known for some time that diet affects the balance of microbes in our bodies, but how that translates into an effect on the host has not been understood. Now, research in mice is showing that microbes communicate with their hosts by sending out metabolites that act on histones—thus influencing gene transcription not only in the colon but also in tissues in other parts of the body. The findings publish November 23 in Molecular Cell.

"This is the first of what we hope is a long, fruitful set of studies to understand the connection between the microbiome in the gut and its influence on host health," says John Denu, a professor of biomolecular chemistry at the University of Wisconsin, Madison, and one of the study's senior authors. "We wanted to look at whether the gut microbiota affect epigenetic programming in a variety of different tissues in the host." These tissues were in the proximal colon, the liver, and fat .

In the study, the researchers first compared germ-free mice with those that have active gut microbes and discovered that gut microbiota alter the host's epigenome in several tissues. Next, they compared mice that were fed a normal chow diet to mice fed a Western-type diet—one that was low in complex carbohydrates and fiber and high in fat and simple sugars. Consistent with previous studies from other researchers, they found that the of mice fed the normal chow diet differed from those fed the Western-type diet.

"When the host consumes a diet that's rich in complex plant polysaccharides (such as fiber), there's more food available for microbes in the gut, because unlike , our human cells cannot use them," explains Federico Rey, an assistant professor of bacteriology at UW-Madison and the study's other senior author.

Furthermore, they found that mice given a Western diet didn't produce certain metabolites at the same levels as mice who ate the healthier diet. "We thought that those metabolites—the short-chain acetate, propionate, and butyrate, which are mostly produced by microbial fermentation of fiber—may be important for driving some of the epigenetic effects that we observed in mouse tissues," Denu says.

The next step was to connect changes in metabolite production to . When they looked at tissues in the mice, they found differences in global histone acetylation and methylation based on which diet the mice consumed. "Our findings suggest a fairly profound effect on the host at the level of chromatin alteration," Denu explains. "This mechanism affects host health through differential gene expression."

To confirm that the metabolites were driving the epigenetic changes, the investigators then exposed germ-free mice to the three short-chain fatty acids via their drinking water to determine if these substances alone were enough to elicit the epigenetic changes. After looking at the mice's tissues, they found that the epigenetic signatures in the mice with the supplemented water mimicked the mice that were colonized by the microbes that thrive on the healthy diet.

Additional work needs to be done to translate these findings from into humans. "Obviously that's a complex task," Denu says. "But we know that human microbial communities also generate these short-chain fatty acids, and that you find them in the plasma in humans, so we speculate the same things are going on."

Rey adds that butyrate-producing bacteria tend to occur at lower levels in people with diabetes and cardiovascular disease, and butyrate is also thought to have anti-inflammatory effects in the intestine.

But the investigators don't advocate supplementing the with short-chain fatty acids as a way around eating healthy. "Fruits and vegetables are a lot more than complex polysaccharides," Rey says. "They have many other components, including polyphenols, that are also metabolized in the gut and can potentially affect chromatin in the in ways that we don't yet understand. Short-chain fatty acids are the tip of the iceberg, but they're not the whole story."

Explore further: Mice fed more fiber have less severe food allergies

More information: Krautkramer et al: Molecular Cell "Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues." http://www.cell.com/molecular-cell/fulltext/S1097-2765(16)30670-0 , DOI: 10.1016/j.molcel.2016.10.025

Related Stories

Mice fed more fiber have less severe food allergies

June 21, 2016
The development of food allergies in mice can be linked to what their gut bacteria are being fed, reports a study published June 21 in Cell Reports. Rodents that received a diet with average calories, sugar, and fiber content ...

Diet lacking soluble fiber promotes weight gain, mouse study suggests

November 2, 2015
Eating too much high-fat, high-calorie food is considered the primary cause of obesity and obesity-related disease, including diabetes. While the excess calories consumed are a direct cause of the fat accumulation, scientists ...

Gut bacteria affect our metabolism

November 21, 2016
Mice that receive gut bacteria transplants from overweight humans are known to gain more weight than mice transplanted with gut bacteria from normal weight subjects, even when the mice are fed the same diet. A study from ...

High dietary fiber intake linked to health promoting short chain fatty acids

September 28, 2015
Eating a lot of fibre-rich foods, such as fruit, vegetables, and legumes—typical of a Mediterranean diet—is linked to a rise in health promoting short chain fatty acids, finds research published online in the journal ...

Friends in low places preserve gut health

January 10, 2014
The bacterial communities that live in our intestines should not be considered freeloaders—they contribute substantially to our well-being in a number of ways, including assisting in the breakdown of otherwise indigestible ...

Short-chain fatty acids in diet stimulate fat utilization

March 6, 2015
(HealthDay)—Short-chain fatty acids (SCFAs), the main products of dietary fiber fermentation, induce a peroxisome proliferator-activated receptor (PPAR) γ-dependent switch from lipid synthesis to lipid utilization, according ...

Recommended for you

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.