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    Food / microbiota interaction in chronic intestinal inflammation

    Team Benoit Chassaing

    Food / microbiota interaction in chronic intestinal inflammation

    In this recent study, mechanisms by which dietary emulsifiers negatively impact the intestinal microbiota and promote intestinal inflammation were elucidated, opening new opportunities for the management of chronic intestinal inflammation. This research was conducted by Benoit Chassaing (team “Mucosal microbiota in chronic inflammatory diseases”) and Emilie Viennois (INSERM U1016/CNRS UMR8104/Université de Paris and INSERM U1149/Université de Paris, respectively). Their findings were published in Cell Reports.

     

    Dietary emulsifiers, often added to a variety of processed foods in order to enhance texture and extend shelf-life, were previously identified to negatively alter the intestinal microbiota in a way that induce intestinal inflammation. It was also previously observed that mice colonized with a microbiota of minimal complexity are protected against emulsifiers negative effects. Those previous findings led us to hypothesize that emulsifiers might provoke some select bacterial members, such as pathobionts (bacteria with pathogenic potential but harmless under “normal” conditions) which could then promote chronic intestinal inflammation and associated diseases, such as colitis-associated cancer.

     

    Germfree (without a microbiota) or ASF (with a minimal microbiota comprising only 8 species) mice were colonized with adherent-invasive Escherichia coli (AIEC), known to be involved in the pathogenesis of Crohn’s disease. Mice were then administered carboxymethylcellulose (CMC – E466) or Polysorbate 80 (P80 – E433).

    While emulsifier consumption was harmless in GF and ASF mice, the combination of AIEC colonization and emulsifier consumption resulted in the development of chronic intestinal inflammation and metabolism dysregulations. Moreover, AIEC colonization resulted in severe intestinal inflammation and exacerbation of colitis-associated cancer in response to emulsifiers consumption in animal models of these diseases. In vitro approaches demonstrated that emulsifier exposure increased the motility of AIEC and its ability to adhere to intestinal epithelial cells. An analysis of the transcriptome (all mRNA transcripts) of emulsifier-treated AIEC revealed that those compounds were inducing the expression of clusters of genes involved in the virulence of this bacterium and in its propensity to induce inflammation. Therefore, these results identify a mechanism by which dietary emulsifiers can promote chronic intestinal inflammation in individuals hosting select pathobionts.

     

    This study is showing that dietary emulsifiers directly rouse the virulence of pathobionts, providing a means by which these compounds may drive inflammation in hosts carrying such bacteria. Importantly, this study also revealed that both tested emulsifiers are not acting in the same manner on pathobionts, suggesting that they can have synergistical detrimental effect when present in combinations, as it is often the case in processed foods. 

    AIEC is probably one example amongst other of a pathobiont driving emulsifier detrimental effects, and the identification of other emulsifier-responsive bacteria is now warranted. Nonetheless, these findings further support the need for microbiota-based dietary intervention in the management of chronic gut inflammation, in which individuals carrying specific microbiota members would greatly benefit from targeted dietary recommendation in order to avoid, for example, such food additives. 

     

    This work was supported by an Innovator Award from the Kenneth Rainin Foundation. Moreover, E.V. is a recipient of the Career Development Award from the CCF and an Individual Fellowship Marie Sklodowska-Curie grant from the European Commission Research Executive Agency. B.C. is supported by a Starting Grant from the European Research Council, a Chaire d’Excellence from Paris University and a Career Development Award from the Crohn’s and Colitis Foundation (CCF).

     

    Reference

    Emilie Viennois, Alexis Bretin, Philip E. Dubé, Alexander C. Maue, Charlène Dauriat, Nicolas Barnich, Andrew T. Gewirtz and Benoit Chassaing.  Dietary emulsifiers directly impact adherent-invasive E. coli gene expression to drive chronic intestinal inflammation.  Cell Reports 2020, 33:108229. https://doi.org/10.1016/j.celrep.2020.108229

     

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