Opportunistic Pathogen that Resides in the Human Gut Linked to Disease

Researchers at the California Institute of Technology (Caltech) have identified a bacterium, Helicobacter hepaticus, that is neither an opportunistic pathogen that causes disease or a beneficial symbiont. Instead, the Caltech researchers, led by Sarkis K. Mazmanian, assistant professor of biology at Caltech, and graduate student Janet Chow, have discovered that this bacterium, depending on the human gut environment in which in resides, can act as either, causing syndromes similar to inflammatory bowel disease (IBD) in immuno-compromised mice or existing harmlessly for years within the human body.

The researchers suspected that the effect of the bacterium’s presence, harmless or otherwise, could be determined “by its ability to communicate with and, more importantly, to modify the immune system of its host.” To test this hypothesis, Chow, lead author of the study published in Cell Host and Microbe, genetically disrupted the secretion system of the bacterium, shutting off this communication. She found that the size of the H. hepaticus population expanded dramatically. This led to dysbiosis, which caused the host immune system to “ramp up its activity,” and inflammation—the body’s response to infection or injury—followed.

"The bacteria appear to have struck a deal with their host," Mazmanian said. “They keep their own numbers low so they don't overwhelm the immune system, and in return, the immune system leaves them alone. The bacteria need the secretion system to put the host in 'don't attack' mode. In return, the presence of the bacteria does not induce inflammation, as would be the case with a pathogen that has not evolved a similar ‘agreement.’”

However, when the communication that keeps this relationship in check is disrupted, the balance is also affected. The change in this balance is what can lead to disease.

"Inflammation leads to cancer, and this bacterium has been associated with inflammation and colon cancer in animals," Mazmanian said. “Understanding if dysbiosis causes disease in humans could lead to therapies based on restoring the healthy microbial balance in the gut.”