Beneficial bacteria may be the key to helping to reverse a cycle of gut inflammation seen in certain inflammatory bowel diseases, University of North Carolina Lineberger Comprehensive Cancer Center researchers have found.

UNC Lineberger researchers compared levels of inflammation in laboratory models with NLRP12, an inflammation regulator, and in models that lacked the gene for this protein.

In a study published in journal Nature Immunology, researchers led by Jenny P.Y. Ting, PhD, Lineberger member and the William Rand Kenan Jr. Distinguished Professor of Genetics, describe how inflammation can go unchecked in the absence of a certain inflammation inhibitor called NLRP12. In a harmful feedback loop, this inflammation can upset the balance of microbiome. They found in preclinical models that certain types of “bad” bacteria were more abundant, while there were lower levels of beneficial bugs in the absence of NLRP12. That led to even more inflammation in their models.

But researchers found that adding back a type of beneficial bacteria that normally grows in the gut can help end this cycle, suggesting a new treatment for inflammatory bowel disease.

UNC Lineberger researchers found a key role for a certain protein called NLRP12 in regulating the inflammation seen in these diseases.

NLRP12 has been known to suppress inflammatory signals to prevent an overactive immune response. But an analysis uncovered low levels of NLRP12 in twins with ulcerative colitis but not in paired twins without the disease. And in mouse models that lacked this protein, they found higher levels of inflammation in the colon.

In the absence of this protein, they also saw changes in the types of bacteria living in the gut – suggesting a role for the protein in keeping the microbiome in balance to prevent inflammation.

“What we found was that these mice not only were missing NLRP12, but they had a completely different composition of bacteria in their gut, and that composition is more pro–inflammatory,” Wilson said.

There were lower levels of “protective,” or friendly strains of bacteria like Lachnospiraceae, and higher levels of bacteria that can help drive inflammation, like Erysipelotrichaceae.

Patients with inflammatory bowel disorder have a similar microbial profile.

“NLRP12 is a checkpoint for the immune system – it checks the level of inflammation,” said Liang Chen, a doctoral student in the Ting lab and the other co–first author on the paper. “If you’re missing that, then you have excessive colon inflammation, and it contributes to disease. But it’s not just the absence of NLRP12, it’s also the interaction of this protein with the gut bacteria.”

To reverse this negative cycle, they found they could add back more of the so–called “friendly” bacteria or use treatments that target inflammatory signals. They believe their findings could potentially lead to treatments for people with inflammatory bowel diseases with reduced NLRP12 expression.