Vaccine Against Bacterial Protein May Lessen Gut Inflammation, Mouse Study Indicates

Vaccinating against flagellin, a protein involved in the movement of certain bacteria, lessened inflammation in the gut, a study of mice shows.

These findings suggest that vaccination against certain bacterial proteins may protect against inflammatory bowel disease (IBD) and other conditions.

“The administration of flagellin, and perhaps other bacterial antigens, has the potential to vaccinate against an array of diseases associated with, and driven by gut inflammation,” Benoit Chassaing, PhD, senior author of the study, said in a press release.

The study, “Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases” was published in the journal Nature Communications.

The human gut microbiome consists of trillions of microbes, primarily bacteria, that reside in our gut. Increasing evidence suggests that alterations to the gut microbiome composition can increase the risk for chronic inflammatory diseases, including IBD.

Previous research has shown that the gut microbiome of people with IBD, including those with ulcerative colitis (UC) and Crohn’s disease, fluctuates more compared to the microbiomes of healthy individuals.

One common change detected in the inflamed gut is an increased production of the protein flagellin, a whip-like appendage that allows bacteria to move and penetrate the intestinal wall. Flagellin also is a potent bacterial antigen (i.e., a protein capable of triggering an immune response).

Researchers at the Institute for Biomedical Sciences and the Neuroscience Institute at Georgia State University investigated whether promoting the body’s production of antibodies against flagellin, a process called immunization and the same principle of a vaccine, could help lessen chronic gut inflammation.

They first immunized mice against flagellin by injecting pure flagellin to the animals’ abdomen for 10 weeks. That triggered the generation of high levels of anti-flagellin antibodies detected in the animals’ blood and stools.

The immunization resulted in less flagellin protein recovered in the animals’  stools compared to control (non-immunized) mice, suggesting that the gut bacteria are less motile and “with less potential to encroach upon host epithelial cells and initiate intestinal inflammation,” researchers wrote.

Moreover, immunization with flagellin altered the intestinal microbiome toward a lower pro-inflammatory state.

Then they tested whether the immunization could help protect against inflammation of the colon (colitis). For this, researchers injected purified flagellin or an innocuous solution into the abdomen of mice for nine weeks followed by a treatment that blocks the signalling of interleukin-10, a process known to trigger colitis.

Both control and flagellin-immunized mice developed symptoms of colitis, including loss of weight, enlarged spleen and colon, and higher levels of inflammation markers, among other features. However, all these symptoms were lessened in mice immunized with flagellin. The immunization also protected against diet-induced obesity.

The results suggest that immunization with flagellin may protect against colitis caused by an altered microbiome and/or imbalance immune response.

“This work is a proof of concept and demonstrates that targeted training of the immune system can protect against an array of chronic inflammatory diseases,” Chassaing said.

“Yet, significant work is now needed to test other antigens, other immunization routes and additional inflammatory models, as well as the human relevance of these findings,” he added.

“If the approach proves translatable to humans, its impact on public health would be enormous,” said study co-author Andrew Gewirtz, PhD, and professor at Georgia State’s Institute for Biomedical Sciences.