Scientists at the University of Minnesota believe they can help people avoid diabetes — one of the nation's most costly and crippling diseases — by salting their intestines with microorganisms from the bowels of healthy donors.
Call it a gut feeling.
It's not as far-fetched as it may sound. Five years ago, U scientists pioneered the technique, known as stool transplants, for the treatment of Clostridium difficile colitis, a potentially deadly diarrheal disease that can result when most of the beneficial microorganisms in the gut get wiped out by antibiotics. It worked in more than nine out of 10 patients.
Now, the U is planning to spend $500,000 in a two-year test to see whether stool transplants could forestall diabetes. The disease has grown dramatically since the mid-1970s and affected 29.1 million Americans, or 9.3 percent of the population, in 2012. Another 86 million adults had "pre-diabetes," a condition caused by the body's insensitivity to insulin, which regulates blood sugar. Preventing diabetes or delaying its onset has the potential to save billions of dollars and reduce the incidence of related diseases affecting vision, the cardiovascular system, kidneys, nerves and skin.
Researchers believe rising obesity rates are largely responsible for the spike in diabetes — hence their interest in digestion.
"Metabolic syndrome, or obesity, that's the biggest prize," said Dr. Alexander Khoruts, a gastroenterologist at the U who will lead the study.
The study, tentatively scheduled to begin recruitment in March, calls for 20 volunteers. Half will get a fecal transplant, by endoscope, from donors with a healthy "microbiome," the community of microorganisms that live in the gut. The other half will get their own microbes back. Drs. Elizabeth Seaquist and Lisa Chow, endocrinologists at the U, will measure the volunteers' sensitivity to insulin before and after the implants.
"The microbes are part of the digestive system," Khoruts said. "They talk to all parts of the human body and participate especially in energy metabolism. That means they tell the human body how much energy to take in — so that's appetite."
They may also explain how the modern American diet affects obesity.
Most of the microbes are found in the lower intestine, where they digest food that wasn't broken down higher in the gastrointestinal track. But a high-calorie diet of fast food and highly processed and sweetened foods gets broken down earlier, leaving few leftovers for most of the microbes.
"So you can imagine that if microbes are not getting fed, they are hungry and they're going to tell the brain, 'Eat more,' " Khoruts said. "We're eating more and we're getting fatter, and the cycle continues."
Eventually, the microbes go extinct, and the only way to fix the problem is a fecal transplant from a lean, healthy donor.
Obese people, studies have shown, have less diverse microbiota than lean individuals. And the microbiota found in remote tribal peoples — who haven't been exposed to antibiotics or processed foods — are far more diverse than those found among urbanites.
Khoruts said that while treating patients for Clostridium difficile, he has seen improvements in some who had been morbidly obese and diabetic, as well as those with anorexia nervosa. But those are just anecdotes.
Animal studies have given researchers reasons to be optimistic that a change in microbes will boost insulin sensitivity and decrease obesity, Khoruts said, and a Dutch study in 2012 suggested that it may be true for humans, as well.
"What we're really trying to do is show this can work in people. It's a proof of principle," Seaquist said.
If the study works, she said, the U would devise a larger study and, ultimately, randomized clinical trials.
The study was funded by MnDRIVE, a $36 million biennial investment fund set up by the U and the Minnesota Legislature to pay for research in robotics and advanced manufacturing, global food supplies, environmental challenges, and brain conditions. The study was funded under a special program that targets projects requiring the collaboration of scientists across multiple disciplines.
"This couldn't be done without the various skill sets," Seaquist said.
Michael Sadowsky, director of the U's BioTechnology Institute, worked with Khoruts on the Clostridium difficile project and will assist on the diabetes study by running fecal samples through DNA sequencing machines to map the genomes of the microbes. The microbes are so complex that supercomputers will be required to analyze the data.
"There are more microorganisms in the human gut than there are stars in the universe," Sadowsky said.
Dan Browning • 612-673-4493
