Bacteria Can Keep Their Kin in Check

Our intestines contain a metropolis of living, thriving bacteria. About 500 species crowd into the large intestine’s unique ecosystem, for example. Most of them are harmless to us—most of the time. But even these ordinarily benign, or commensal, bacteria may contribute to certain bowel disorders, past research has suggested.

Now, scientists have evidence that the mammalian gut can be fortified to resist the occasional disruptions of resident microbes. To keep bacteria in check, Mary H. Perdue of McMaster University in Hamilton, Ontario, and her colleagues fed laboratory rats a special dietary supplement.

Its key ingredient? Yet more bacteria.

Such beneficial bugs, called probiotics, are the focus of a booming field of medical research. Findings suggest that certain bacterial strains can guard the body against a variety of ills. (For examples, see “Flora Horror,” “Germs That Do a Body Good,” and “Spray Guards Chicks from Infections.”)

In the new study, Perdue’s team used commercially available strains of Lactobacillus helveticus and Lactobacillus rhamnosus that are sold together in powder form. The researchers dissolved the powder in water and made sure the organisms were alive.

Then, for 17 days, the team gave the mixture to some lab rats and sterile drinking water to others. Both groups of animals ate normal lab-rat chow throughout the experiment.

A week into that regimen, the researchers began subjecting the rats to what rodent researchers call water-avoidance stress.

They placed each animal on a small platform in the middle of a small pool. The animals weren’t in danger of drowning, but during each hour-long test they also couldn’t leap to dry land from their island of safety.

“Rodents have a natural aversion to water, and they become very anxious if they can’t escape,” Perdue says. The water-avoidance exercise, she says, “is a purely psychological stressor.”

The rats experienced the stressful test each day for the final 10 days of the experiment.

Stress and sickness

Psychological stress can have negative effects on people’s intestinal health. Stress has been linked to irritable bowel syndrome and symptoms of Crohn’s disease. Long-term stress is also associated with relapses of ulcerative colitis, an inflammatory bowel disorder.

Perdue says that stress encourages commensal bacteria to adhere to the intestinal wall and alters the wall’s permeability, making it “leaky.” When bacteria slip out of the gut and reach other tissues, the body may overreact with a damaging inflammatory response.

Perdue’s team designed its study to probe whether probiotics might bolster the gut’s protection against the effects of stress. After giving the rats the probiotic mixture or plain water for 17 days, the researchers inspected the animals’ guts.

In animals that had drunk plain water, about 100 bacteria clung to each square millimeter of the tissue’s inner walls. By comparison, in rats that had received probiotics, two portions of the intestines had 14 and 21 bacteria, on average, per square millimeter, the researchers report in an upcoming Gut.

Rats that hadn’t been subjected to stress had no bacteria adhering to their intestinal walls, the researchers report.

Perdue and her colleagues also removed and dissected lymph nodes to which gut-escaping bacteria tend to migrate. Animals that had received the probiotics before and during the period of chronic stress had no bacteria in the targeted lymph nodes. By contrast, the corresponding nodes from other animals contained an average of more than 1,000 germs.

“The probiotic bacteria that we gave the animals completely prevented the penetration of commensal bacteria through the intestinal wall,” Perdue reports. “The probiotics appear to be forming a protective layer over the surface of the intestine.”

“The probiotics are protecting the intestine from the dysfunction that arises from stress,” agrees gastroenterologist Michael Camilleri of the Mayo Clinic in Rochester, Minn.

But the coating effect that Perdue describes may not be the main contributor to the reduction in bacterial escape, Camilleri adds. Rather, probiotics may increase intestinal cells’ production of mucus or of immune-system proteins called immunoglobulins, he says.

Data from the study indicate that stressed animals’ intestines remain leaky regardless of whether the animals receive probiotics, he notes. Further research will be needed to explain the apparent discrepancy between that fact and the protective effect of the probiotics, he says.

The research has potential clinical applications in inflammatory disorders such as Crohn’s disease and pouchitis, which can be a complication of Crohn’s or ulcerative colitis, Camilleri says.

“There is increasing evidence of a minor inflammatory state in irritable bowel syndrome,” he says, so probiotics might make a difference in that condition, too.

“We don’t want to make too big a jump,” Perdue cautions. “But it’s certainly possible” that probiotics might help people with irritable bowel syndrome.

Products that claim to contain probiotics are widely available, but Perdue offers some caveats.

“Most of them have not been tested in a scientific manner. And a lot of them probably don’t do anything because the bacteria might be dead or might not be present in sufficient numbers,” she says.

On the other hand, she adds, “probiotics don’t do any harm.”

Eventually, she predicts, “we’ll have different mixtures of probiotics to treat different conditions.”