Seeking to reduce the risk of chronic inflammation, Inserm researchers stimulated the production of anti-flagellin antibodies in mice to reduce the presence of flagellin-expression bacteria in the gut microbiota. The research was published today in Nature Communications.
Chronic inflammatory bowel diseases, such as Crohn’s Disease and ulcerative colitis, are linked to abnormalities of the gut microbiota. Patients generally present with reduced bacterial diversity in their intestinal flora along with excessive levels of bacteria that express a protein called flagellin, which favors their mobility, enabling these bacteria to penetrate the layer of mucous that covers the usually sterile intestinal wall. The purpose of this layer is to form a bacteria-resistant wall between the internal digestive tract and the rest of the body, thereby protecting it from the risk of inflammation linked to the presence of the billions of bacteria of the intestinal flora.
Previous research has already shown that antibodies are naturally found within this mucous layer, some of which are directed against flagellin. In the current study, the researchers administered flagellin to mice intraperitoneally, thereby inducing a marked increase in the anti-flagellin antibodies, particularly in the intestinal mucosa. The researchers then applied a protocol in order to induce chronic intestinal inflammation, after which they observed that immunization against flagellin gave the animals significant protection from intestinal inflammation.
Given that excess flagellin in the gut microbiota has also been linked to metabolic disorders such as diabetes and obesity, the researchers tested their vaccine strategy in mice exposed to a high-fat diet. While the unvaccinated animals developed obesity, the vaccinated animals were protected.
“This vaccine strategy can be envisaged in humans, because such abnormalities of the microbiota have been observed in patients with inflammatory and metabolic diseases,” says senior author Benoit Chassaing. “With this in mind, we are currently working on a means of locally administering flagellin to the intestinal mucosa.”
The researchers are considering the possibility of developing ingestible flagellin-filled nanoparticles. Finally, in addition to the preventive aspect, they now wish to test this vaccination for treatment purposes in animals already presenting chronic inflammatory disease or metabolic disorders.