Bacteria study: It's a gut check

Pam Lowney

Les Dethlefsen needs volunteers for a study that will identify intestinal bacteria.

In sheer numbers, the bacteria that live inside of us outnumber our own cells tenfold. They perform tasks that are beneficial (processing nutrients, helping store fat and providing protection against invading pathogens) and harmful (being a potential source of infection, creating carcinogens and triggering chronic illnesses).

The prevalence of these tiny organisms has inspired Les Dethlefsen, PhD, a postdoctoral scholar in microbiology and immunology at the School of Medicine, to try to identify the many varieties found in the human body and to see how these communities of microbes change over time.

"We have co-evolved with the organisms and communities inside of us, certainly for the hundreds of millions of years that animals have had guts," said Dethlefsen. "We have this phenomenally complex ecosystem inside of us, yet we know so little about how we interact with these internal inhabitants."

Dethlefsen is seeking volunteers for a yearlong study to track the stability of the microbial community in the large intestine and to see how that community is affected by an antibiotic. Participants will provide monthly stool samples for most of the year with more frequent sampling surrounding two periods of antibiotic use.

To survey the hundreds of types of bacteria living in the colon, Dethlefsen will take every stool sample and sequence a gene that all bacteria share in common. Minor differences in the gene sequence allow individual identification of the bacteria in these samples.

Two months into the study, and again six months later, volunteers will take a five-day course of the antibiotic Cipro (generically known as ciprofloxacin) that will kill off some types of bacteria, but which is not lethal to most of the microbes in the intestine. With the help of the genetic sequencing, the researchers hope to document Cipro's effects on the whole community of bacteria living in the colon, not just the ones directly sensitive to the drug.

"Our study really takes the form of a classical ecological perturbation study," said Dethlefsen. As an example, he compared their work to that of a field ecologist who puts two fence enclosures around an area of a meadow; one enclosure would be sealed and the other open on one end to allow animals through. The scientist could then compare what happens to plant species with and without grazing. In that example, Dethlefsen said, ecologists are studying both direct and indirect effects that ripple through the ecosystem.

"We are looking at Cipro as a perturbation of the intestinal ecosystem, and if we see any effects, it will likely be those that are rippling through the ecosystem rather than the direct effects of drug," he said.

Previous studies of bacteria in culture indicate that the effects of antibiotics, even those much more potent than Cipro, are no longer seen after two to six weeks, and the microbial environment returns to normal. "Or at least it appears to be normal," said Dethlefsen. He outlined several scenarios in which a second dose of an antibiotic might elicit a response that could indicate some "memory" of an earlier antibiotic exposure. He designed his study to have the participants take Cipro twice to see if he can observe any such residual effect.

Dethlefsen works with David Relman, MD, associate professor of medicine (infectious diseases and geographic medicine) and of microbiology and immunology. Relman emphasized that Cipro poses minimal risk to study participants.

The study's findings might have ramifications for general widespread antibiotic use. "It may be that in the not-too-distant future, we look at the indiscriminate use of antibiotics much like we look back at the indiscriminate use of pesticides in agriculture," Dethlefsen said. "It may be that we open the door to further problems down the road, even as we solve an immediate problem."

He added, "That's why it's worth knowing about the ecosystem of the gut, so we can use the knowledge to our advantage."

Volunteers will be compensated $200 for their time in the study, which is funded by the Ellison Medical Foundation. Call Dethlefsen at 493-5000, ext. 63193, for more information or to volunteer. Relman's lab is located at the Veteran Affairs Palo Alto Heath Care System.