New study offers insight into how stomach fights infections

A new study is offering clues as to how the stomach fights off infections – a discovery that could someday help people suffering from conditions like irritable bowel disease (IBD).

Researchers, including Bruce Vallance, an associate professor at the University of British Columbia and a scientist at the Child & Family Research Institute at BC Children's Hospital in Vancouver, British Columbia, have long been interested in studying what happens when bad bacteria, such as salmonella, infiltrates the gut.

In a study published in PLOS Pathogens, Vallance and his team honed in on a previously discovered protein called SIGIRR, which seemed to suppress normal immune responses in the gut. They were curious to see if eliminating SIGIRR would allow the gut to fight off infections more successfully.

To test their theory, the researchers engineered a group of SIGIRR-free mice and then injected them with small amounts of disease-causing bacteria.

“In the absence of this protein, we expected the gut to respond more strongly, trigger inflammation and kill the remaining (bad) bacteria,” Vallance said.

However, they saw something much more surprising.

“Instead of killing bad bacteria, it killed the good bacteria,” Vallance said. “If you do that, then the bad bacteria can spread throughout the intestines and cause severe infection.”

This drastically changed the researchers’ view of SIGIRR. Instead of limiting the body’s ability to fight infection, the protein actually acts as a restraint on the body’s inflammatory response, allowing the gut’s good bacteria to have a chance to fight off the infection instead.

When bad bacteria enters a healthy gut, it has to compete with trillions of good bacteria for nutrients and space. In a healthy person, the good bacteria will typically be able to fight off bad pathogens. Only in rare cases will the good bacteria fail, triggering a last-ditch inflammatory response strong enough to kill off both good and bad bacteria.

“The dogma is that inflammation helps kill off infections, and that can be true,” Vallance said. “But in the gut, because we have so many normal bacteria…in that case inflammation isn’t good in intestines. It doesn’t help us fight off pathogenic bacteria. It may actually make us more susceptible (by killing off the good bacteria too).”

Though more research needs to be done into SIGIRR, Vallance and his colleagues hope this discovery might eventually provide a pathway to help people who suffer from frequent stomach infections.

“In some cases, there may be people out there who have less SIGIRR than others. They may be more susceptible to gut infections or IBD,” Vallance said. “If we can regulate SIGIRR in patients with IBD, we might limit inflammation and promote the reestablishment of good bacteria.”