Researchers led by Dr Benoît Chassaing, Inserm researcher at Institut Cochin (Inserm/CNRS/Université de Paris), have a developed a vaccine
for animals that modify the the composition and function of the gut microbiota, providing protection against the onset of chronic inflammatory bowel diseases
and certain metabolic disorders
, such as diabetes
and obesity. Their next step is to develop a similar vaccine for humans.
The research findings have been published in the journal of Nature Communications
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.
Past 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.
Finding ways to reduce the risk of chronic inflammation
, Inserm researcher Benoit Chassaing and his colleagues 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.
The medical 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
, 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.
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.
Dr Chassaing told
News, "This vaccine
strategy can be envisaged in humans, because such abnormalities of the microbiota have been observed in patients with inflammatory
and metabolic diseases
. With this in mind, we are currently working on a means of locally administering flagellin
to the intestinal mucosa."
The medical 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
Reference : Hao Q. Tran et al, Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases, Nature Communications (2019). DOI: 10.1038/s41467-019-13538-y