What happens when good gut microbes go bad? You get IBD

Inflammatory bowel disease (IBD) isn’t likely caused by a single microorganism, researchers have found. Rather, an otherwise harmless bacterium in the gut works together with gut microbiota to instigate the inflammatory reaction.

Surprisingly, the bacterium itself, Helicobacter bilis, doesn’t become a target of the immune response it instigates, researchers reported in a recent study published in Scientific Reports. Instead, the immune response attacks other gut bacteria—and even when researchers removed some of those bacteria, the immune response continued unabated.

“What hasn’t been reported in the literature is that there are organisms, like the Helicobacter in this example, that contribute to the disease process but are not overt targets of that process,” said lead researcher Amanda E. Ramer-Tait, PhD, Harold and Ester Edgerton Assistant Professor of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.

Dr. Ramer-Tait and colleagues chose to study H. bilis because it’s a pathobiont—a bacterium that lives a benign and symbiotic lifestyle in the gut under usual circumstances, but can activate during episodes of inflammation to exacerbate the inflammatory disease process.

“Under normal conditions, the immune system tolerates gut bacteria,” Dr. Ramer-Tait explained. “But sometimes there are breaks in the intestinal barrier because of either a genetic susceptibility or an environmental trigger, which is similar to creating a hole in a fence. That breach then increases the likelihood that the immune system will launch an attack.”

To study this kind of attack, the researchers replicated these conditions in mice. Using a colitis-inducing salt (dextran sulfate sodium) as an environmental trigger, they confirmed that the H. bilis pathobiont works synergistically with gut microbiota to induce inflammatory disease.

Remarkably, the inflammatory response didn’t react against H. bilis, but to other gut bacteria instead.

“The ability of H. bilis to incite (immune) responses against the microbiota, but not itself, is a novel finding that may partly explain why no single microorganism or immune response against particular microbiota members has ever been associated with inflammatory bowel diseases,” the researchers wrote. “Even more striking is our observation that severe pathobiont-mediated intestinal inflammation does not appear to depend on any specific member of the microbiota.”

This finding could significantly change how IBD is diagnosed because it suggests that testing for changes in immune responses to gut microbiota may be of far greater diagnostic value than testing for responses to a specific pathobiont or bacterium in the microbiota.

In short, this study shows that one specific microorganism probably isn’t solely responsible for IBD, Dr. Ramer-Tait explained.

“That idea has been a big focus in the field for years, because people have been looking for the microbe that contributes to disease. However, it may be that certain features shared by multiple microbes are perpetuating disease instead. Perhaps we should be looking for those characteristics as opposed to trying to identify a specific causative agent,” she said.

“What makes a good microbe go bad? That’s the question I think we should be asking.”

Funding for this study was provided by the National Institute of Health’s Institute of General Medical Sciences and the Crohn’s and Colitis Foundation of America.