Repeated antibiotics alter beneficial gut germs

[September 15, 2010]  WASHINGTON (AP) -- Antibiotics can temporarily upset your stomach, but now it turns out that repeatedly taking them can trigger long-lasting changes in all those good germs that live in your gut, raising questions about lingering ill effects.

Nobody yet knows if that leads to later health problems. But the finding is the latest in a flurry of research raising questions about how the customized bacterial zoo that thrives in our intestines forms -- and whether the wrong type or amount plays a role in ailments from obesity to inflammatory bowel disease to asthma.

Don't be grossed out: This is a story in part about, well, poop. Three healthy adults collected weeks of stool samples so that scientists could count exactly how two separate rounds of a fairly mild antibiotic caused a surprising population shift in their microbial netherworld -- as some original families of germs plummeted and other types moved in to fill the gap.

It's also a story of how we coexist with trillions of bacteria, fungi and other microbes in the skin, the nose, the digestive tract, what scientists call the human microbiome. Many are beneficial, even indispensable, especially the gut bacteria that play an underappreciated role in overall health.

"Gut communities are fundamentally important in the development of our immune system," explains Dr. David Relman of Stanford University, who led the antibiotic study published Monday in Proceedings of the National Academy of Sciences. "Let's not take them for granted."

Next, Relman plans to track whether antibiotics used during the first year or two of life, when youngsters form what will become their unique set of gut bacteria, seem to predispose children later to immune-related diseases.

Antibiotics already should be used cautiously because they can spur infection-causing bacteria to become drug-resistant. The new research raises different questions about effects on beneficial bacteria -- and if abnormalities in the microbiome really are linked to health problems, how those changes might begin.

"We should start paying attention to this," says Dr. Martin Blaser, a microbiome specialist at New York University Langone Medical Center, who wasn't involved with Relman's work but also is planning to study the issue in children. "The main point is that antibiotic use is not free in a biological sense."

Everyone is born with an essentially sterile digestive tract, but within days the gut is overrun with bacteria from mom and dad, the environment, first foods. Ultimately, a healthy person's intestinal tract teems with hundreds of species of microbes, the body's biggest concentration, with many involved in such things as digestion and immune reaction.

In the not-so-healthy, scientists have discovered that overweight people harbor different types and amounts of gut bacteria than lean people, and that losing weight can change that bacterial makeup. They've also found links to other digestive diseases, precancerous colon polyps -- and even are pursuing a theory that early use of antibiotics disrupts the developing microbiome in ways that spur autoimmune disorders like asthma or allergies.

Antibiotics aren't choosy and can kill off good germs as well as bad ones. But Relman and fellow research scientist Les Dethlesfsen wondered how hardy gut bacteria are, how well they bounce back. So they recruited healthy volunteers who hadn't used antibiotics in at least the past year to take two five-day courses of the antibiotic Cipro, six months apart.

The volunteers reported no diarrhea or upset stomach, yet their fecal samples showed a lot going on beneath the surface. Bacterial diversity plummeted as a third to half of the volunteers' original germ species were nearly wiped out, although some other species moved in. Yet about a week after stopping the drug, two of the three volunteers had their bacterial levels largely return to normal. The third still had altered gut bacteria six months later.

The surprise: Another die-off and shift happened with the second round of Cipro, but this time no one's gut bacteria had returned to the pre-antibiotic state by the time the study ended two months later.

"History matters," concludes Relman, whose next is testing what jobs the most affected bacteria performed -- such as helping to maintain intestinal barriers against infection -- and whether the new bugs fully replaced them. "We may have to be more careful" about repetitive damage, he said.

Of course, antibiotics aren't the only means of disrupting our natural flora. Other research recently found that babies born by cesarean harbor quite different first bacteria than babies born vaginally, offering a possible explanation for why C-section babies are at higher risk for some infections. Likewise, the gut bacteria of premature infants contains more hospital-style germs than a full-term baby's.

The big issue is when such differences will matter, something that so far, "we're not really smart enough to know," Relman says.

[Associated Press; By LAURAN NEERGAARD]

Lauran Neergaard covers health and medical issues for The Associated Press in Washington.

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