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

Make way for hemoglobin

August 18, 2017
Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

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.