Mysteries of the Microbiome

A U of M associate professor explores the complex world of human microorganisms and the cures they may hold

Mysteries of the Microbiome

Dr. Alexander Khoruts understands if you hesitate to shake his hand. He does dirty work. But he's saving lives with what the rest of us flush away.

The University of Minnesota associate professor is part of a revolution that's overturning decades of scientific assumptions in acknowledging the critical role of bacteria in managing our health.

Though officially a gastroenterologist/immunologist, in reality Khoruts is more of a microscopic wildlife manager. He attempts to restore the gut-flora system of those wracked with Clostridium difficile, or C. diff, a gastro-intestinal affliction.

Dr. Alexander Khoruts at the U of M is a leading researcher in the new science of the microbiome
E. Katie Holm
Dr. Alexander Khoruts at the U of M is a leading researcher in the new science of the microbiome
Ellen Bolte (left) dedicated herself to helping son Andy (middle) recover from autism-like symptoms
Ellen Bolte (left) dedicated herself to helping son Andy (middle) recover from autism-like symptoms

C. diff typically strikes those who are hospitalized and given antibiotics. Sufferers get the runs until they literally run out. Death usually occurs from dehydration. With 15,000 to 20,000 deaths per year from C. diff, the disease claims more lives in the U.S. annually than HIV.

Khoruts's treatment involves a simple, straightforward procedure dating back to fourth-century China, but which has only found sporadic acceptance until recently. It's called a fecal transplant.

Healthy donors come to his office and leave a sample of the rich diversity in their gut and colon. Khoruts liquefies, filters, and freezes it for future study or transplant.

Khorut's lifesaving stool transplants are just the first application made possible by our emerging understanding of the microbiome, the 100 trillion or so microorganisms that inhabit the body, particularly the gut. There are 10 times as many microbial as human cells, and their DNA is both more diverse and plentiful than our own by a hundredfold.

These bacteria, viruses, fungi, and other microorganisms that evolved inside of us over the course of millions of years appear to play such an important role in our biology that they've been collectively dubbed "the forgotten organ."

"I was an immunologist, I like to think I still am in some ways," Khoruts says from the office adjoining his old immunology lab on the University of Minnesota campus. "Within my clinical sub-specialty a whole new organ was just accepted. I have to drop whatever I am doing and focus on that because that is never going to happen again."

Not only do our microbiota facilitate digestion, but they've also been linked to mental health, allergies, auto-immune diseases, heart disease, and various cancers. Where genes evolve over generations, our microbial ecosystem responds and adapts much quicker to environmental stressors or changes.

The microbiome appears to work epigenetically (turning genes on or off) and in concert with our immunological system to keep us healthy. While we've long heard about pathogenic bacteria, the great majority of bacteria in our body perform beneficial functions.

Some create enzymes we can't. For example, there are plentiful complex oligosaccharides in breast milk, which humans lack the enzyme to break down. But it's food for some species of beneficial gut bacteria that turn it into nutrients the baby can use. This fuels the growth of good gut bacteria, which squeezes out the pathogens, keeping them isolated.

This is just a small example of how our bodies and bacteria have co-evolved. But Khoruts and other researchers increasingly believe that widespread use of antimicrobial agents and antibiotics — along with our Western diet — are damaging our hard-won gut flora. It may be the key factor in a wide range of recent epidemics including obesity, diabetes, Crohn's disease, and even autism.

"The diversity of our microorganisms is decreasing," Khoruts says, "with possibly deleterious consequences like the emergence of these diseases."

Two years ago Catherine Duff's life was hardly a life at all. She was suffering her seventh bout of C. diff in six years, beset by abdominal pain, fever, loss of appetite, and chronic diarrhea that would strike 20 to 30 times a day.

"My bed is about maybe 15 feet from the toilet in our bathroom," says the 57-year old mother of three who lives in Indianapolis. "I had to have a potty chair beside the bed."

The only time she left the house was to go to the hospital, which she had to do almost every other day. Over the course of 10 to 12 hours, she'd get 12 to 15 bags of saline and bags of enriched plasma to boost her busted immune system.

The line between dehydration and death can be thin, so she had a network of friends who took turns checking in on her while her husband was at work.

"They would come over and I wouldn't be making any sense. They'd say, 'Come on, we have to get some fluids in you.' This was my life for months at a time," Duff recalls. "You literally feel your life draining out of you."

Duff first caught C. diff in 2005 after a diverticulitis attack whose treatment went south to the point where she had to have a temporary colostomy. They removed part of her colon and had to treat her with broad spectrum antibiotics because the wound became infected.

Duff would catch C. diff five more times, in each instance treating it with stronger antibiotics as it became harder and harder to eradicate. Eighty percent of the time you treat C. diff with antibiotics and it goes away. It recurs for 20 percent, and each time it does means the disease is two to three more times likely to return.

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