Good Bug/Bad Bug
The two faces of Helicobacter pylori
A funny thing happened to Helicobacter pylori, the bacterium that causes gastric cancer or peptic ulcers in up to 15 percent of the people it infects. After decades of work to develop a vaccine and plans for a global vaccination campaign, scientists now have evidence that it might not be such a bad bug, after all. In fact, for most people, there could be benefits to having H. pylori living in your stomach.
“Until recently the consensus was that the only good H. pylori are dead H. pylori,” says John Y. Kao, M.D., a U-M gastroenterologist and assistant professor of internal medicine. “But 85 percent of infected individuals have no symptoms and never develop cancer or ulcers. We want to know if there’s anything good about these bacteria before we talk about wiping them out.”
More than half the world’s population is infected with H. pylori. Most people are infected early in childhood, especially among families living in crowded, unsanitary conditions. The bug spreads via fecal-oral, oral-oral or gastric-oral transmission.
“The global incidence of H. pylori infection has been declining for the last two decades,” says Kao. “The decline has been attributed to a cleaner environment, testing and treatment, but as the rate of H. pylori infection goes down, rates of chronic inflammatory diseases like asthma, allergies and inflammatory bowel disease are going up.”
Kao and his team discovered there’s a connection between H. pylori and the immune system. They found that H. pylori down-regulates inflammation in its human host by causing certain immune cells to shut down production of pro-inflammatory molecules called cytokines. Suppressing the immune system helps the bacteria avoid the body’s normal attack-and-kill response to bacterial infection. Kao wondered if the bug’s innate ability to dampen down the immune system could explain why cases of inflammatory bowel disease (IBD) like ulcerative colitis or Crohn’s disease increased as cases of H. pylori infection went down. He assigned three researchers from his lab to work on the problem.
One was Jay Luther, M.D., then a second-year resident in internal medicine who had received an NIH grant to do research in basic science. The second, Stephanie Owyang, was an Ann Arbor high school student who had received an award from the American Gastroenterological Association to work in Kao’s lab during the summers. Min Zhang, M.D., a research specialist in Kao’s lab, assisted with the project.
Luther and Owyang analyzed DNA from different strains of H. pylori, E. coli and other bacteria. They found that DNA from H. pylori contained more regulatory sequences known to reduce an inflammatory response. DNA from E. coli and other pathogens had more DNA sequences known to stimulate an inflammatory response. When added to cultures of dendritic cells grown in the laboratory, H. pylori DNA suppressed production of pro-inflammatory cytokines.
The next step was to determine if H. pylori DNA could suppress inflammation in laboratory mice with colitis, an acute inflammation of the colon. The researchers fed H. pylori DNA to one group of mice with colitis and E. coli DNA to a second group. Mice given H. pylori DNA had significantly less diarrhea, bleeding and inflammatory changes in the colon than mice in the control group or mice given E. coli DNA.
As a final step, the researchers measured levels of type 1 interferon, an inflammatory cytokine, in blood serum from 46 healthy men. The 22 men who were infected with H. pylori had lower levels of this pro-inflammatory molecule in their system than men without H. pylori.
Kao emphasizes that he’s not suggesting physicians start infecting their patients with H. pylori. He hopes this research will highlight the potential negative consequences of global vaccination programs against H. pylori and support the current practice of treating only people with symptoms. He hopes to identify the H. pylori DNA sequences with potent anti-inflammatory effects and use them to develop a new therapy for patients with IBD and other chronic inflammatory diseases.
“This could be a way to give patients the beneficial effects of H. pylori without causing any of its complications,&rdqo; Kao says. “If you give only these genetic sequences, the bug cannot colonize the stomach, so there’s no concern about cancer or ulcers.” —SALLY POBOJEWSKI
For the published research study
For patient information on inflammatory bowel disease
