Researchers develop way to alter intestinal microbiota, vaccinate against inflammatory diseases

A new study by the Institute for Biomedical Sciences and the Neuroscience Institute at Georgia State University found that targeted immunization against bacterial flagellin (a protein that allows bacterial movement) can beneficially alter the intestinal microbiota. This decreases the bacteria's ability to cause inflammation and then protects against chronic inflammatory diseases. 

The study, published in the journal Nature Communications​, suggests this approach can be used to vaccinate against diseases such as inflammatory bowel diseases, obesity, and metabolic syndrome. The intestinal tract is colonized by billions of beneficial bacteria, but improperly controlled microbiota can lead to chronic inflammatory diseases.

The research was funded by the Crohn's and Colitis Foundation, the Kenneth Rainin Foundation, the National Institutes of Health and the European Research Council.

Enormous impact 

"If the approach proves translatable to humans, its impact on public health would be enormous,"​ added co-author Dr. Andrew Gewirtz, a professor in Georgia State's Institute for Biomedical Sciences.

Therapeutic options have focused on decreasing the inflammatory response while failing to acknowledge the contribution of the intestinal microbiota contributions. The scientists aimed to determine if a targeted immune response could be used to beneficially shape the intestinal microbiota and protect against inflammatory diseases. 

Previously, the researchers found that a common feature of microbiotas associated with inflammation is an increased level of expression of flagellin by select microbiota members, which can drive bacteria to penetrate the intestinal mucosa and disrupt homeostasis.

Previous studies have shown the intestinal microbiota are associated with inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, and diseases characterized by low-grade inflammation of the intestinal tract, such as obesity and metabolic syndrome.

Study details 

The report hypothesized that “boosting levels of mucosal flagellin-specific IgA might help keep flagellated bacteria in check and, consequently protect against development of chronic gut inflammation.”​

With that in mind, the scientists immunized mice with flagellin to bring out an adaptative immune response. From there they were able to demonstrate targeted immunization against bacterial flagellin is sufficient enough to beneficially alter the composition and function of the intestinal microbiota. The mice produced anti-flagellin antibodies and reduced the microbiota’s inflammatory inclinations and ability to penetrate its host. These alterations tied to protection against chronic inflammatory diseases.

Dr. Benoit Chassaing, senior author of the study and assistant professor in the Neuroscience Institute and the Institute for Biomedical Sciences at Georgia State and team leader at the National Institute for Health and Medical Research and the Universite de Paris in Paris, France, told NutraIngredients-USA that the results weren't entirely surprising: "We knew that flagellated bacteria are playing a role in the promotion of inflammation. So we expected that targeting such flagella with directed Immunization can be beneficial - but we were pleased by the strength and the reproductibility of the beneficial microbiota modulation,"​ adding, "We think this is an innovative approach, since it is targeting one factor causing inflammation instead of targeting the inflammation itself."​

Potential, but more research needed 

"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,"​ said Dr. Chassaing."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. 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."​

Dr. Chassaing told NutraIngredients-USA that they are currently ​working on way to specifically immunize the intestinal comportment as well as planning to identify a human sub-population that may benefit from such an approach.

Source: Nature Communications​
10, 5650 (2019) doi.org/10.1038/s41467-019-13538-y​​
“Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases”​
Authors: Tran, H.Q., et al.