Preventing microbiota bacteria from penetrating the intestinal barrier is the goal of this new vaccine developed by French researchers to fight chronic intestinal diseases. Tested on mice, the vaccine would protect them against inflammatory diseases but also against obesity and diabetes, a strategy that, according to them, is conceivable in humans.
Several chronic intestinal diseases, such as Crohn’s disease, are associated with an imbalance in the bacterial flora of our intestines, the microbiota. Patients often have a reduced bacterial diversity within their microbiota. By modifying the composition of the microbiota with a vaccine, the team of Benoît Chassaing, a researcher at the Cochin Institute, has protected mice from these chronic inflammatory diseases. The first results of this study were published in Nature Communications.
A vaccine that interferes with the mobility of bacteria in the microbiota
Some bacterial species that evolve in our intestines overexpress Flagellin, a protein that constitutes the flagellum, a structure that allows bacteria to be mobile. The flagellum allows them to perforate the layer of mucus that covers the intestinal wall. This normally sterile layer forms a bacteria-tight wall between the digestive tract and the rest of the body, protecting it from the inflammatory risk associated with billions of bacteria in the digestive tract.
Previous work has shown that antibodies are naturally present within this mucus layer, some of which are directed against the flagellin. This means that the body spontaneously develops immune protection against it, which controls the presence of the bacteria that express it.
Benoit Chassaing’s team came up with the idea of stimulating this production of anti-flagellin antibodies by means of a flagellin vaccine. The aim is to reduce the risk of chronic inflammation caused by the bacteria by neutralizing their means of locomotion. The researchers administered the peritoneal flagellin to mice, thus inducing a strong increase in anti-flagellant antibodies, particularly in the intestinal mucosa. They found that immunization against flagellin significantly protected the animals from intestinal inflammation.
In addition, a fine analysis of the microbiota and their intestines showed, on the one hand, a reduction in the amount of bacteria expressing flagellin strongly and, on the other hand, the absence of these bacteria in the intestinal mucosa, unlike the unvaccinated group.
An effective vaccine against diabetes and obesity
The abundance of mobile bacteria in the intestinal microbiota is also associated with metabolic disorders such as diabetes and obesity. The researchers then tested their vaccination strategy on mice with a high-fat diet.
This vaccination strategy is possible in humans.
While unvaccinated animals developed obesity, vaccinated animals were protected. “This vaccination strategy is feasible in humans since such microbial abnormalities have been observed in patients with inflammatory and metabolic diseases. To this end, we are currently working on means of locally administering the flagellin to the intestinal mucosa,” explains Benoît Chassaing.
For example, researchers are considering the possibility of developing unmanageable flagellin-filled nanoparticles. Finally, beyond the preventive aspect, they now want to test this vaccination in a curative way, on animals that already suffer from chronic inflammatory diseases or metabolic dysfunction.