Dr. Johannes Aas was stumped.

The patient in his Duluth clinic was not responding to antibiotics, and now the stubborn infection in his intestines threatened to kill him. Then Aas found a similar case written up in a 1950s Norwegian medical journal.

The cure? Replace all the bacteria in the patient's gut with a tiny dose of someone else's stool.

(Warning to readers: The rest of this story requires a strong stomach -- but it provides a remarkable glimpse into the medical potential of the unseen universe inside us.)

The cure that Aas discovered that day worked almost instantly, but other doctors scoffed. Well, they are not scoffing anymore.

With the proliferation of dangerous superbugs that are resistant to antibiotics, the unusual treatment is gaining respect from researchers across the country.

That shift in thinking reflects a growing regard for the complex and largely unknown bacterial ecosystem inside the human body.

The "microbiome,'' as it is known, is now the focus of a $115 million federal research project to investigate the symbiotic bond between humans and their bacteria.

"People's appreciation for the microbiome has changed," said Dr. Alex Khoruts, a gastroenterologist and associate professor of medicine at the University of Minnesota. "It's a fascinating frontier."

Marauders take over

Aas' patient 10 years ago had a common intestinal infection caused by a bacterium called C. difficile. It sometimes takes hold when patients get a dose of antibiotics for some other reason. These can destroy the population of beneficial intestinal bacteria, or flora, that digest food and provide nutrients to the body. Then the spores of C. difficile, which can lurk in the gut, flower and take over, producing a toxin that causes severe diarrhea and, in time, destroys the colon lining.

Often, a dose of a different antibiotic will suppress the infection. But sometimes C. difficile just keeps coming back.

"I was so, so, so sick," said Keri Primbs, 34, of California, who was treated for a C. difficile infection in Duluth in 2006. "I had diarrhea 20 times a day." The infection lasted on and off for a year. She and her husband "nicknamed it the beast."

Patients like Primbs used to be rare. But C. difficile is one of a growing number of micro-organisms that have become resistant to antibiotics, while at the same time becoming more common and virulent. According to the U.S. Centers for Disease Control and Prevention, hospitalizations from C. difficile infections increased by 23 percent each year between 2000 and 2005. Death rates tripled between 1999 and 2004.

Aas and his colleagues at the St. Mary's Duluth Clinic, like other doctors around the country, began seeing more and more patients who just couldn't get rid of the infection. Aas, at least, had a solution.

"If the normal flora in the colon is destroyed, in my book, you replace it," said Aas, a gastroenterologist who is now semi-retired.

With what? With someone else's flora.

The little brown bag

The procedure is not as bad as it sounds. More important, by the time people need one, they'll do anything to get rid of their infection. Janet Jolliffe, 49, of Pennsylvania, is a case in point.

"This is nothing compared to what I've been through," she said in September during a visit to Minnesota.

She is one of about 60 patients who have found their way to Duluth for stool transplants -- a unique sort of medical tourism for northern Minnesota. She and many others found out about it through www.cdiffsupport.com, an online support group.

On a crisp fall day, she sat in the exam room with an opaque tube running through her nose, down her throat and into her stomach.

"We just need that little brown bag," said Dr. Timothy Rubin, a gastroenterologist who works with Aas. He meant the stool sample from Jolliffe's husband, which was being processed in the lab. It was mixed with water and filtered to take out the organic matter, leaving a dark brown liquid that contained billions of bacteria.

When the little bag arrived with the sample inside, Rubin used a large syringe to inject the liquid through the tube and into Jolliffe's stomach. It was over in less than a minute.

"All I felt was cold," she said.

Rubin says that when Aas first told him about the procedure he thought it was, unusual, yes, but also brilliant. "He kept it simple, inexpensive and available to anyone," he said.

Symbiosis

Now, Rubin and Aas are researching which bacteria are the critical players in the hidden war inside the gut. If they can answer that, patients might one day get a pill with the right bacteria instead of a tube in their nose.

Khoruts, the university gastroenterologist, recently did his first stool transplant. The patient was an older woman whose C. difficile infection was so bad that she had to live in a diaper. Instead of a nose tube, he gave her a liquid stool enema. Within days, she was better.

"It was striking," he said. Now, he and microbial ecologist Mike Sadowsky at the university are starting a similar research project to identify the crucial bacteria.

Aas says he doesn't know exactly why the stool transplant works. He presumes that the infusion of donated flora resets the bacterial balance in the gut and somehow keeps the C. difficile in check. Whatever the mechanism, it works 95 percent of the time.

Neither group of researchers expects that finding the answer would result in a new, blockbuster drug. There are probably not enough severe cases for that kind of payoff. They are after different stakes -- a better understanding of the relationship between humans and their bacteria.

Who are we?

The human body is a universe of microflora living in vast numbers in harmony on the skin, in the mouth and elsewhere in the body. By far, the largest number live in the intestinal tract. "It's one of the densest bacterial populations known on Earth," Khoruts said. "It's its own ecosystem."

If researchers can discover more about the workings of this "microbiome,'' they might open an entirely new frontier of medical treatments. Recent research has revealed tantalizing glimpses into the role microflora might play in everything from obesity to preventing cancer. It's been shown that overweight people have different bacteria than those of normal weight.

But almost nothing is known about how many species there are, what jobs they perform, or how they differ from person to person, group to group.

The first thing, Sadowsky said, is to identify the different species, which is the focus of a research project funded by the National Institutes of Health. Researchers across the country are embarking on a bacterial genome project much like the human genome project, which identified all the genes in the human body.

"You can isolate all their DNA, use it to ask questions about physiology, and to understand who the players are and what there functions are," Sadowsky said.

It's an acknowledgement that the human genome project ignored the crucial part played by the billions of microscopic lives that share our bodies.

The critical question, scientists now say, is not "who am I," but "who are we."

Josephine Marcotty • 612 673 7394