Cold and Flu : Using Good Bacteria to Beat Bad Bacteria

Mark Roth

Thirty years ago, Andrew Goldberg encountered the Earwax Man.

As a young intern in Pittsburgh training to be an ear, nose and throat physician, Dr. Goldberg met a middle-aged patient who had recurring infections in one ear.

Dr. Goldberg and his colleagues would give him antibiotic drops, and the problem would go away. But then it would come back -- until one day, when the man walked in and claimed the infection had disappeared.

"We just assumed that one of our myriad drop regimens had finally hit its mark and wiped out the guy's bacteria," said Dr. Goldberg, who now oversees sinus surgery at the University of California at San Francisco Medical Center.

The man knew otherwise. "You see," he told the doctors, "I figured, I have one ear that's bad and one ear that's good, and whatever's in my good ear I want to get over to my bad ear, so I just took some wax from my good ear and put it in my bad ear and within a couple days, I was fine."

The Human Microbiome

Dr. Goldberg just laughed uncomfortably at the man's explanation back then. But today, he believes the patient was right: By putting earwax from one ear into the other, he was also transferring the bacterial colonies from the healthy ear into the sick one, and that probably cured his persistent infections.

This strange story is now a legend in the fast-growing field known as the human microbiome -- the study of the trillions of bacteria that live inside us and the critical role they play in our health and in many of our diseases.

In recognition of their importance, the National Institutes of Health has established the Human Microbiome Project, an ambitious effort to comprehensively catalog the microbes living in several parts of our bodies. There is also research going on at labs around the world to investigate what role bacteria might play in several chronic diseases, and there's even a quirky educational venture in North Carolina known as Belly Button Biodiversity.

Here's a look at just a few of the microbiome projects.

Chronic sinus infections

Dr. Goldberg's latest research focuses not on ears, but sinuses.

Like his Pittsburgh patient, many people with chronic sinus infections can't get rid of them despite repeated doses of antibiotics and cleanouts of the infected cavities, which sit behind the nose, cheeks, eyes and forehead.

Using new genetic analysis techniques, Dr. Goldberg and his colleagues found in a study published last year in Science that 10 patients with recurring infections had about 300 fewer species of bacteria in their sinuses than 10 healthy patients did -- 900 vs. 1,200.

They also found the sick patients had depleted ranks of a benign species of bacteria known as Lactobacillus sakei, and elevated populations of a species known as Corynebacterium tuberculostearicum.

The findings were made possible by a new tool called the PhyloChip, which allowed researchers to analyze the genetic material of all the bacteria taken from the patients, instead of just the species that were able to grow in the laboratory.

Often, only a handful of all bacteria in a sample can grow in a laboratory dish, Dr. Goldberg said, and "who's to say that what grows on an agar plate is the most important bacterium in that environment?"

Infectious disease specialists used to think persistent bacterial infections were caused by biofilms -- gooey layers that shielded the bacteria from antibiotics.

"The idea was that if we could just kill the hiding bacteria, everything would be fine," he said. "But that's clearly only part of the issue, because if you don't reconstitute a [healthy bacterial] environment that will be self-sustaining, you're right back to your old problem."

Dr. Goldberg's team found that mice infected with the C. tuberculostearicum species could be cured by giving them the helpful L. sakei strain, which kept the harmful bacteria in check.

One day, he believes, similar "probiotic" treatments with beneficial bacteria might be used to cure chronic sinus infections in people.

Intestinal ailments

The microbiome-based treatment that has received the most publicity is fecal transplants to cure chronic intestinal infections caused by the Clostridium difficile bacteria.

Despite the "ick factor," the transplants, in which a doctor puts liquefied feces from a healthy donor into the intestines of a sick patient, have been incredibly successful.

In a study last month in the New England Journal of Medicine, European doctors found that 13 of 16 C. difficile patients who got fecal transplants no longer had diarrhea, compared with just four of 13 who got the antibiotic vancomycin.

Patients often get C. diff infections, as they're known informally, after repeated antibiotic treatments, which deplete both helpful and harmful bacteria in the intestines.

The thinking, said Paul Lebovitz, who heads up the Allegheny Center for Digestive Health at Allegheny General Hospital, is that "C. diff is normally held in check in patients because there are good bacteria that keep it in check, but with frequent antibiotic use, you basically destroy the good bacteria and the normal balance that exists in the gut goes out of whack and allows the C. difficile to grow and become infectious."

After taking a year to develop the procedure, Dr. Lebovitz has done two fecal transplants in Pittsburgh. For now, he is confining them to C. difficile patients who are hospitalized and resistant to antibiotics. He uses a colonoscopy tube to transfer the feces from healthy donors to the patients.

He believes bacteria in the gut may turn out to play a critical role in several diseases, including Crohn's, inflammatory bowel disease, rheumatoid arthritis and even heart disease.

"In fact, I think the future of health care will be about the gut microbiome," he said.

Obesity

If bacteria in the intestines can play a role in disease, can they also be a factor in obesity?

Some animal studies suggest that might be true. In the lab, mice bred to be germ-free don't gain extra weight, but when the bacteria from the guts of obese mice are transferred to their bodies, the germ-free mice get fat on the same diets they consumed before.

At New York University, researchers found that mice given small doses of antibiotics put on 10 to 15 percent more fat than mice that did not get the drugs, suggesting that the antibiotics were altering the rodents' microbiome.

Fredrik Backhed, a researcher at the University of Gothenburg in Sweden, said studies of bacteria and obesity in humans have been more ambiguous, but he believes the microbes could play a part in our tendency to gain weight, along with our own genetic makeup, diet and lack of exercise.

It would make sense, he added, that the bacteria that evolved along with human beings over the eons would be more likely to help us gain weight than lose it.

"In our early history as human beings, getting obese or having diabetes wasn't an issue, but not getting enough food was a big problem, so we probably evolved a microbiota that was very efficient in making use of energy" from food.

Navel gazing

It's not just that our bodies house thousands of different kinds of bacteria, but they differ widely depending on where they set up shop.

On our skin, tough species like Micrococcus and Staphylococcus epidermis dominate.

That's one of the findings of the quirky Belly Button Biodiversity project at North Carolina State University and the North Carolina Museum of Natural Sciences, both in Raleigh.

The project began a couple of years ago, when one laboratory worker wanted to send out a holiday card with pictures of the lab staff's skin microbes. Before they knew it, they were setting up tables at science fairs and other public events to collect bellybutton bacteria from passers-by, said Rob Dunn, a biology professor and author of "The Wildlife of our Bodies: Predators, Parasites and Partners That Shape Who We Are Today."

The group now has navel bacteria samples from hundreds of people. Its analysis has shown this quiet little neighborhood on the body houses up to 2,000 different species of bacteria, but just like trees in a tropical rainforest, only a few species tend to dominate.

At the same time, Mr. Dunn said, the dominant species on you might be entirely different from those on your neighbor, and so far, no factor -- age, gender, location or whether you're an innie or an outie -- seems to determine which bacterial group you fall into.

"If you pick any two people, their microbes on their skin will differ, and one will have healthier microbes than another, but we don't know how to measure that yet or manage it.

"Even if you think bellybuttons are stupid, your own bellybutton microbes and those all over your body directly affect your health and well-being. It's shocking to me every time I dig into this that we are so ignorant about the species that live on us and around us, and yet we wake up to them every day."

Mark Roth: mroth@post-gazettecom or 412-263-1130.

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