Man's best friend? New take on infection-causing bugs

Stanley Falkow

Bacteria are bad. Mothers and doctors, not to mention the cleaning product industry, warn of their dangers. But a medical school microbiologist is raising an intriguing idea: Persistent bacterial and viral infections have benefits.

Stanley Falkow, PhD, the Robert W. and Vivian K. Cahill Professor in Cancer Research, published an essay on this topic in the Feb. 24 issue of the journal Cell, in which he asks, "Is persistent bacterial infection good for your health?" The essay is based on a talk he gave at Cambridge University in November.

Falkow points out that the medical community and those who fund medical research focus on curing disease. He wonders if this single-mindedness might distract researchers from appreciating micro-organisms' contributions.

"Organisms that cause disease are usually considered in the context of harm and epidemics," he said. "But the fact is that a great number of organisms that infect humans come in and set up housekeeping as it were. There are no clinical symptoms of anything wrong, and people take the organisms with them to their graves."

It's not that the organisms in question—such as the bacteria that cause pneumonia or meningitis—are innocuous, he said. It's just that most individuals do not get disease from being infected.

The best recent case of this, said Falkow, is Heliobacter pylori. The bug earned researchers the 2005 Nobel Prize in Medicine or Physiology for implicating it as a cause of ulcers and stomach cancer. As is typical in microbiology, though, it's not a simple equation: Being infected = ulcers or cancer. At least 80 percent of the world is infected with H. pylori yet has no overt symptoms.

What makes the study of H. pylori even more perplexing is that as advances such as clean water and pasteurization are adopted, the prevalence of H. pylori infection has declined. On the one hand, this has been accompanied by a drop in the incidence of gastric cancer and ulcers. On the other, there has been an increase in esophageal cancer. H. pylori appear to protect against cancer of the esophagus. "That says that there might be something about persistent infection that might be protective," said Falkow.

This raises the conundrum: By messing with the microbes, are we just replacing one disease with another?

Falkow's lab has been studying the phenomenon of persistent infection for decades, in particular with H. pylori and Salmonella. He and his colleagues have shown that when infected with these organisms, mice initially show an inflammatory response that then settles down and stays with them for the rest of their lives.

Although few of these organisms remain in the mice, it is enough to cause the immune system to have an ongoing response. "It's not so much that the immune system has failed," Falkow explained, "but that the organisms have manipulated the immune system in such a way that they can't be cleared." If the infections are cleared by antibiotic intervention, the mice are highly susceptible to re-infection, and the re-infection is more likely to progress to disease.

Furthermore, as many infectious diseases have decreased, autoimmune diseases such as ulcerative colitis, Crohn's disease and diabetes have increased.

"All these observations have been made without necessarily trying to pull it all together," said Falkow. "What I tried to do in this article is point out that the continued presence of these organisms may actually be beneficial to the host and that is why they are tolerated by the immune system."

It's an idea that requires more research in animal models. "We don't know what to look for per se," he said. "But we can guess that since a persistently infected host is constantly having its immune system stimulated and refined, that may provide it with resistance to other things."

He wondered whether, as with H. pylori, humans are unknowingly causing other microbes to disappear that have been present for ages and that may have health benefits. "Could it be this is responsible for some of the things we see such as the failure of the immune system to act appropriately?" he asked.

The only answer to date is: "It's complicated." Instead of a persistent infection, some people get very ill from organisms such as Salmonella, H. pylori, tuberculosis and meningitis. How the immune system responds differently in individuals demands further research.

Falkow credits his colleagues for providing the fodder for his essay.