In a new study, researchers have developed a new vaccine against chronic inflammatory diseases.
They found this vaccine could modify the composition and function of the gut microbiota.
It provides protection against the start of chronic inflammatory bowel diseases and certain metabolic disorders, such as diabetes and obesity.
The research was conducted by a team at Institut Cochin (Inserm/CNRS/Université de Paris)
Chronic inflammatory bowel diseases, such as Crohn’s Disease and ulcerative colitis, are linked to abnormalities of the gut microbiota in humans and in animals.
Patients generally present reduced bacterial diversity in their intestinal flora along with excessive levels of bacteria that express a protein called flagellin, which favors their mobility.
This enables them to penetrate the layer of mucous that covers the intestinal wall and which is usually sterile.
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 had already shown that antibodies are naturally found within this mucous layer, some of which are directed against flagellin.
This means that the body spontaneously develops immune protection against flagellin, making it possible to control the presence of the bacteria that express it.
Seeking to reduce the risk of chronic inflammation, the team had the idea of stimulating this anti-flagellin antibody production in order to reduce the presence of the bacteria that express flagellin in the gut microbiota.
They 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, whereupon they observed that immunizing against flagellin gave the animals significant protection from intestinal inflammation.
In addition, detailed analysis of their microbiota and intestines revealed not just a reduction in the levels of bacteria that strongly express flagellin but also their absence in the intestinal mucosa, as opposed to the unvaccinated group.
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.
Whereas the unvaccinated animals developed obesity, the vaccinated animals were protected.
The team says this vaccine strategy can be envisaged in humans because such abnormalities of the microbiota have been observed in patients with inflammatory and metabolic diseases.
The study is published in Nature Communications.
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