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    A new approach to modulate intestinal microbiota and vaccinate against chronic inflammatory diseases

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    A study of Benoit Chassaing's team

    The team “Mucosal microbiota in chronic inflammatory diseases”, in a study published in Nature Communications,

    demonstrates that an innovative approach of immunization allowed to modulate the murine intestinal microbiota in a beneficial way, protecting against the development of chronic inflammatory diseases. This work was performed in collaboration with Andrew Gewirtz from Georgia State University and Ruth Ley from Max Planck Institute.

     

    The gastrointestinal tract is colonized by billions of bacteria and other microorganisms, collectively called microbiota, which play many beneficial roles. If this microbiota is not kept under control by its host, it can promote the development of chronic inflammatory diseases such as ulcerative colitis, Crohn's disease, or a metabolic syndrome.

    So far, therapeutic options have focused on decreasing the inflammatory response and have often neglected the contribution of the gut microbiota. In this study, researchers wanted to determine whether a targeted immune response could be used to beneficially modulate intestinal microbiota and protect against inflammatory diseases.

    Indeed, they had previously found that one of the features common to microbiota associated with inflammation, is an increase in the expression of flagellin by some members of the microbiota. Since flagellin is the main component of bacterial motility organs (flagella), its increase allows some bacteria to invade the mucus layer protecting our intestinal epithelium and normally sterile (see figure), thus inducing chronic inflammation.

     

    Figure legend: Observation of the murine colon by confocal microscopy. The bacteria of the microbiota are visualized in red, the intestinal mucus in green, the actin of the intestinal cells in purple and their DNA in blue.

     

    In this study, mouse models were immunized with flagellin to induce an adaptive immune response and such targeted immunization was sufficient to modify both the composition and function of the intestinal microbiota in a beneficial manner. Anti-flagellin antibodies were produced and affected the microbiota by reducing its pro-inflammatory potential and its ability to penetrate the mucus layer.

     

    In a murine model, these microbiota alterations were associated with protection against intestinal inflammation and against certain metabolic dysregulations. Thus, these results suggest that targeting certain members of the microbiota - particularly their flagellin - may offer an innovative way to vaccinate and protect against chronic inflammatory diseases of the digestive tract.

      

     

    This work is a proof of concept, and further work is now needed to test other antigens, other means of immunization, as well as the relevance of these results to humans.

     

    The study is funded by the Crohn's and Colitis Foundation, the Kenneth Rainin Foundation, the National Institutes of Health and the European Research Council.

     

    Reference

    Tran HQ, Ley RE, Gewirtz AT, Chassaing B. Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases. Nat Commun. 10, 5650 (2019) doi:10.1038/s41467-019-13538-y

     

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