From mice, clues to microbiome's influence on metabolic disease

February 17, 2017 by Terry Devitt
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

The community of microorganisms that resides in the gut, known as the microbiome, has been shown to work in tandem with the genes of a host organism to regulate insulin secretion, a key variable in the onset of the metabolic disease diabetes.

That is the primary finding of a study published this week (Feb. 14, 2017) in the journal Cell Reports by a team led by University of Wisconsin-Madison researchers Alan Attie and Federico Rey. The new report describes experiments in mice showing how genetic variation in a host animal shapes the microbiome—a rich ecosystem of mostly beneficial microorgannisms that resides in the gut—and sets the table for the onset of metabolic disease.

"We're trying to use genetics to find out how bugs affect diabetes and metabolism," explains Attie, a UW-Madison professor of biochemistry and a corresponding author of the new study.

Peeling back the complex interplay of , diet and the trillions of microorganisms that live in the guts of humans and other animals, Rey, Attie and their colleagues are beginning to work out the subtleties of how host genes shape the composition of the microbiome and contribute to an animal's phenotype and, ultimately, diet-induced .

Metabolic diseases such as diabetes have long been known to be influenced by both genes and diet. Understanding the role of the microbes that live in the gut and help process nutrients not only promises a fuller understanding of the link between genes, diet and disease, but may also be a pathway to pinpointing the genes responsible for conditions like diabetes.

"We're asking whether or not there is a chain of causality between and (disease) phenotype," says Attie. "Genetics is the anchor. If something is associated with a gene, it is truly a causal relationship, not just a correlation."

To leverage that approach, the new Wisconsin study employed a cohort of eight strains of mice whose genetics collectively mirror the genetic diversity of the human population.

"These mice show tremendous phenotypic diversity," says Attie. "Some are lean. Some are susceptible to obesity. Some are resistant to obesity. Some of these phenotypes can be partially transmitted by gut microbiota."

Clues to the influence of genes on the composition of the microbiome emerged from experiments where mice were raised in a germ-free environment and challenged by a diet high in fat and sugar. Through fecal transplants, microbiomes could be effectively traded bewteen strains, helping researchers home in on the interplay between genes and the microbiome.

"Our study suggests that a lot of the we see among these eight strains of mice is reflected in their microbiomes," notes Rey, a UW-Madison professor of bacteriology and a corresponding author of the study. "And we have evidence that the composition of the gut microbiota is controlled by the genomes of the mice. We're trying to find the genes that control the composition of the gut microbiota and (dictate) host phenotype."

In response to diet, the Wisconsin group observed a "remarkable variation" in whose genetics make them prone to diabetes. They also noticed an accompanying change in the makeup of the animals' gut microbiomes. Some of the bacteria, according to Rey and Attie, could be linked to metabolic traits such as body weight, and glucose and insulin levels.

The microbiome plays a crucial role in processing nutrients. Food not metabolized directly by a host like a mouse or a human is subsequently processed in the gut by the bacteria of the microbiome. As the microbes metabolize food, they produce an astonishing number of small molecules, chemicals and hormones that circulate in a host and can influence health in an animal.

Among those metabolites, perhaps as many as 20,000 in all, are what are called short-chain fatty acids, which serve as signaling molecules in the intestine and associated organs like the liver and pancreas. In particular, they are key regulators of energy and glucose.

Gut microbes also influence the physiology of the host by modifying bile acids produced by the liver, which are also processed by the microbiome to produce secondary metabolites that can exert an influence on disease and health.

Mice in the study that were put on a rich diet and received microbiome transplants helped the Wisconsin team expose functional differences attributable to two different transplanted microbiomes, including a link between the and .

Explore further: How important is the gut microbiome? It may depend on your genetics

Related Stories

How important is the gut microbiome? It may depend on your genetics

November 7, 2016
Our gut microbiomes—the bacteria that live in our digestive tract—play major roles in our health. Scientists around the world are studying therapies that manipulate the microbiome, including probiotics (such as live bacterial ...

Genes, early environment sculpt the gut microbiome

November 28, 2016
Genetics and birthplace have a big effect on the make-up of the microbial community in the gut, according to research published Nov. 28. in the journal Nature Microbiology.

Changes in the diet affect epigenetics via the microbiota

November 23, 2016
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 ...

'FishTaco' sorts out who is doing what in your microbiome

January 19, 2017
A growing body of evidence indicates that the trillions of microbes that live on and inside our bodies affect our health. Collectively, these resident microbes form our microbiome.

Gut microbe movements regulate host circadian rhythms

December 1, 2016
Even gut microbes have a routine. Like clockwork, they start their day in one part of the intestinal lining, move a few micrometers to the left, maybe the right, and then return to their original position. New research in ...

Major finding identifies nitrogen as key driver for gut health

November 23, 2016
Scientists are one step closer to understanding the link between different diet strategies and gut health, with new research presenting the first general principles for how diet impacts the microbiota.

Recommended for you

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Estrogen discovery could shed new light on fertility problems

December 12, 2017
Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

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.