US scientists have opened up a new and novel pathway to vaccinating the body against inflammatory bowel diseases – as well as protect against diet-induced obesity and metabolic syndrome, the cluster of conditions that increase your risk of heart disease, stroke and type 2 diabetes.
It’s well established that changes to intestinal microbiota are associated with inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. But metabolic diseases such as obesity are also characterised by low-grade inflammation of the intestinal tract.
“An array of chronic inflammatory diseases are associated with dysbiosis (microbial imbalance) in the intestinal microbiota and a breakdown in the normally mutually beneficial host–microbiota relationship,” the authors write.
Most treatments for chronic inflammatory diseases – such amino-salicylates, antibiotics and corticosteroids – target the inflammation.
The researchers, from Georgia State University, have instead, essentially, cut the tails off bacteria – thus impeding their motility – that compromise the digestive tract and prompt debilitating inflammatory responses.
Here’s how they did it and what it means
Bacteria commonly move about with the aid of flagella, whip-like structures that flick the single-cell along – or are sometimes, in a cluster, swirl together like a propellor.
Flagella are made up of a protein called flagellin – it was this protein the scientists focused on.
Why? Because when people develop conditions such as Crohn’s disease and ulcerative colitis, they tend to have a reduced bacterial diversity in their intestinal tract – an abnormality that leads to excessive levels of flagellin.
This allows super-charged bacteria to infect the layer of sterile mucous that covers the intestinal wall and is designed to protect the digestive tract from inflammation.
The body already produces flagellin antibodies within the mucous layer, to defend against destructive bacteria. The Georgia State researchers decided to investigate whether this defence mechanism could be boosted sufficiently via a vaccine.
And lo, they had success
According to a statement from the university, the researchers repeatedly injected experimental mice with flagellin “to elicit an adaptive immune response and demonstrated targeted immunisation against bacterial flagellin is sufficient to beneficially alter the composition and function of the intestinal microbiota”.
“Anti-flagellin antibodies were produced and affected the microbiota by reducing its pro-inflammatory potential and ability to penetrate its host. These alterations were associated with protection against chronic inflammatory diseases,” the university wrote.
In other words, gut health was improved, microbe diversity was boosted and the protective mucous layer was less vulnerable to invasion.
The mice were also found to be protected against obesity.
The findings of the study suggest that “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 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.
“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 immunisation routes and additional inflammatory models, as well as the human relevance of these findings.”
Co-author D. Andrew Gewirtz, a professor in Georgia State’s Institute for Biomedical Sciences said: “If the approach proves translatable to humans, its impact on public health would be enormous.”