Vaccine against intestinal diseases
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are associated with abnormalities of the microbiome – billions of bacteria living in the intestinal lumen. Usually, there is a decrease in bacterial diversity in the intestinal flora along with an excessive increase in the number of bacteria that express the flagellin protein that promotes their mobility. Flagellin allows bacteria to penetrate through the mucous layer that covers and protects the intestinal wall. The task of this layer is to create a barrier between the bacteria inside the intestine and the body, protecting it from inflammation that the intestinal flora can cause.
Previous studies have shown that antibodies are naturally detected in the mucous layer, including against the flagellin protein. This means that the body independently forms an immune defense against flagellin, controlling the bacteria that express it.
Confocal microscopy of the colon. The microbiome is marked in red, the intestinal mucosa is green, the intestinal cells are purple, their DNA is blue. Source: article in Nature Communications.
In order to reduce the risk of chronic inflammation, Benoit Chasing and his group from the National Institute of Health and Medical Research (Institut national de la santé et de la recherche médicale, Inserm) in France decided to stimulate the production of anti-flagellin antibodies in order to reduce the number of flagellin-expressing bacteria in the intestinal microbiome.
Researchers injected mice with flagellin intraperitoneally, causing a noticeable increase in the number of antibodies against it, especially in the intestinal mucosa. The researchers then induced chronic intestinal inflammation in the mice. They noticed that immunization against flagellin gave the animals substantial protection against inflammation. In addition, a detailed analysis of their microbiome revealed not only a decrease in the level of bacteria expressing flagellin, but also their absence in the intestinal mucosa, unlike mice of the unvaccinated group.
Given that excess flagellin in the intestinal microbiome is also associated with metabolic disorders such as diabetes and obesity, the researchers tested their vaccination strategy in mice fed a high-fat diet. While the unvaccinated animals developed obesity, the vaccinated animals were healthy.
This vaccination strategy may be effective in humans, because the described microbiome disorders are observed in patients with inflammatory and metabolic diseases. Currently, the group is working on a method of local administration of flagellin into the intestinal mucosa. The researchers are also considering the possibility of developing absorbable nanoparticles filled with flagellin. Finally, in addition to the preventive aspect, they intend to test the effectiveness of vaccination in a therapeutic mode on animals that already have chronic inflammatory bowel disease or metabolic disorders.
Article Q.Hao et al. Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Inserm Press Room: A Vaccine Against Chronic Inflammatory Diseases.