From diabetes, asthma and tooth decay to lake algae, dairy production and panda reproduction, UW-Madison researchers are studying how tiny bugs in our guts, our mouths and a variety of ecosystems help or harm.
A new initiative on campus will award up to $1 million in grants to scientists who study microbiomes — communities of bacteria, viruses, fungi and other microorganisms that live in humans, other animals and the environment.
The goal is to bring in additional federal money and explore how health, agriculture, climate and other interests are influenced — and possibly can be improved — by living things we can see only under a microscope.
With microbes increasingly viewed as powerhouses of biology, new technology available to sequence their genes and the announcement last year of a National Microbiome Initiative, the time is right for UW-Madison to step up its efforts, said Jo Handelsman, director of the university’s Wisconsin Institutes for Discovery.
“It’s seen as an area of growth for science and for industry and for academic pursuit,” Handelsman told UW-Madison researchers last year, when she was associate director for science in the White House Office of Science and Technology Policy.
“More and more disease is thought to be treatable by changing the microbiome, but we don’t have a clue how to do that in humans,” Handelsman said in an interview last week, in which she said microbiomes also can affect how people respond to drugs.
“Maybe someday you’ll be able to get a simple test of your microbiome and know which of five drugs is more likely to work on you,” she said.
As faculty from a variety of fields prepare to apply by March 15 for grants through UW-Madison’s Microbiome Initiative, many are already analyzing how microbes interact with people and the world.
About 20 faculty members have microbiome research grants from federal agencies or other organizations, worth a total of about $8 million a year.
Microbes and insulin
For Alan Attie, a professor of biochemistry, the focus is diabetes, a disease associated with obesity that involves impaired manufacturing or use of the hormone insulin. Studies have suggested links between gut microbes and obesity, though findings have been mixed.
Attie works with Federico Rey, an assistant professor of bacteriology, in using mice to study insulin production. They gave several strains of mice a diet high in fat and sugar, causing one strain to become obese and develop signs of diabetes while a genetically different strain remained lean and healthy.
The researchers transplanted feces, containing gut microbiomes, from the two groups of mice into a third group raised in isolation to be germ-free, without microbiomes.
The transplant recipients, when given the same diet, developed conditions similar to their donors. After meals high in sugar, or glucose, insulin levels spiked in one group but not in the other, the researchers reported last month in the journal Cell Reports.
“The microbes that colonize the gut control how much insulin the mouse secretes when it encounters glucose,” Rey said.
Christine Sorkness, a UW-Madison pharmacist, has studied the relationship between the lung microbiome and asthma.
Other medical conditions thought to be influenced by microbes include autism, heart disease and some cancers.
Athletes and cavities
Dental cavities could also be related to microbiomes. In recent years, some studies have yielded a surprising finding: elite athletes seem to get more cavities than other people, even though they are healthier in other ways.
Melissa Christopherson, a faculty associate in bacteriology, examined why last year by asking UW-Madison athletes and students from her microbiology class to contribute saliva samples and fill out questionnaires.
The microbiology students compared the mouth microbiomes of the two groups, looking at a host of factors that could contribute to oral health, such as smoking, mouthwash, caffeine and use of an electric toothbrush.
“There were no variables that made a huge difference except for being an athlete,” Christopherson said.
Athletes’ microbiomes had different quantities of three species of microbes, a finding that now can be explored further.
Participants in the Wisconsin Longitudinal Study — a decades-old effort assessing success, health and aging by following thousands of high school graduates from the class of 1957, as well as some of their spouses and siblings — are used to giving up samples of saliva, blood and urine.
Two years ago, some were asked to join the microbiome craze and contribute their feces. About 450 participants, or 78 percent of those asked, said yes.
“They were really great about it,” said Pamela Herd, a professor of public affairs and sociology who directs the study. It is sometimes called the “Happy Days cohort,” after the 1970s television sitcom set in Milwaukee in 1957.
With help from Rey’s lab, where feces samples are stored in coolers at minus 80 degrees Celsius, Herd learned that gut microbiomes of married couples are more similar, and apparently healthier, than those of siblings. Additionally, microbiomes of married couples who report close relationships are more similar, and apparently healthier, than those of married couples who don’t say they’re close.
Lakes and soil
Trina McMahon, a professor of bacteriology and civil and environmental engineering, is looking beneath the water, comparing microbiomes in Lake Mendota with those from two lakes north of Minocqua: Sparkling Lake and Trout Bog Lake.
She is studying how cyanobacteria — or blue-green algae, a human health concern — intermingle with other bacteria in fresh water, and how light and temperature influence various microbe populations.
Another project in McMahon’s lab involves the Madison Metropolitan Sewerage District’s Nine Springs wastewater treatment plant. She and other campus researchers are studying microbes that remove nitrogen or phosphorus, which can make Madison’s lakes mucky in summer, from sewage.
Currently, the plant pumps compressed air into wastewater to feed the bacteria that remove the nutrients.
“If you could reduce the amount of compressed air you have to add, you could save a lot of money and reduce the carbon footprint,” McMahon said.
Handelsman, the Wisconsin Institutes for Discovery director who is also a former chairwoman of UW-Madison’s bacteriology department, studies microbiomes in soil, focusing on erosion and carbon storage.
Soil contains more carbon than all of the Earth’s plants, or the atmosphere, Handelsman said.
“If we’re going to have a large impact on climate change and carbon concentrations, we have to be considering the microbes in soil,” she said.
Dairy and bamboo
Garrett Suen, an assistant professor of bacteriology, studies microbiomes in cow stomachs and panda poop.
Using cows at the U.S. Dairy Forage Research Center in Prairie du Sac, Suen examines microbiomes in rumen, one of a cow’s four stomachs. He’s searching for ways to increase milk production or alter milk composition to improve quality.
In a new experiment, Suen is altering the microbiomes of calves, before many microbes colonize their rumen, to see if that influences their milk.
With pandas, Suen’s research suggests the animals might not be good at digesting one of their favorite foods: bamboo.
Pandas in captivity periodically stop eating and shed their gastrointestinal tract linings in their stool. The episodes often occur when females are pregnant, impeding reproduction.
Working with the Memphis Zoo, Suen compared microbiomes in regular panda feces with those in the abnormal feces, called mucoids. He found key differences and suspects bamboo’s sharp edges might be injuring pandas’ gastrointestinal tracts. Some zookeepers are considering alternative foods for pandas.
“Maybe this is one of the reasons why it’s challenging for pandas to reproduce in captivity,” he said.
“Maybe someday you’ll be able to get a simple test of your microbiome
and know which of five drugs is more likely to work on you.” Jo Handelsman, director of the UW-Madison’s Wisconsin Institute for Discovery