Institut de recherche biomédicale
     
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    Equipe : Interactions microbiote/mucus dans les maladies inflammatoires chroniques

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    Responsable

    Our research interest is to understand the roles played by the intestinal microbiota in health and diseases, with a focus on intestinal inflammation and metabolic disorders.

    Our intestinal tract is colonized by a complex community of microorganisms, named microbiota, which is playing numerous beneficial roles. However, uncontrolled microbiota can lead to detrimental impacts on its host by promoting chronic intestinal inflammation and associated diseases. In our laboratory, we are investigating how the intestinal microbiota is regulated by environmental factor, such as food additives (Axis 1), as well as how the host and its microbiota communicate (Axis 2). We are also exploring innovative ways to beneficially modulate the intestinal microbiota in order to promote health (Axis 3).

     

    Objectives

    Axis 1 - Environmental factors-mediated modulation of the intestinal microbiota

    We are highly interested in studying some environmental factors that can alter the intestinal microbiota. We have previously reported that emulsifiers, highly used by the food industry, are able to detrimentally alter the intestinal microbiota, characterized by an increased ability to penetrate the normally protective mucus layer and an increase pro-inflammatory potential. We reported that the consumption of emulsifying agent is sufficient to induce intestinal inflammation that will manifest as chronic colitis in genetically susceptible host. Moreover, in unimpaired host, such food additives are inducing the development of metabolic syndrome characterized by diabetes and an increase in body weight, as well as by an increased susceptibility to colonic carcinogenesis.

    Our ongoing research on this area is focusing on the mechanisms beyond such observations:

    • how dietary emulsifiers are able to directly impact the intestinal microbiota?
    • how the altered microbiota will subsequently drive deleterious phenotypes?

     

    Axis 2 - Innate immunity / microbiota relationship in health and disease

    We have studied for many years how the host is controlling the intestinal microbiota in order to keep it under control and at a proper/safe distance from the intestinal mucosa. We have for example demonstrated that the flagellin receptor TLR5 is playing a central role in keeping the intestinal microbiota under control. Animals lacking the TLR5 receptor develop intestinal inflammation that can manifest with the development of chronic colitis or metabolic syndrome. In the liver, we have recently demonstrated that TLR5 is playing an important protective role during western-style diet consumption.

    Our current research is focusing on:

    • characterizing the microbiota members driving intestinal inflammation
    • identifying some therapeutic approaches to beneficially alter the intestinal microbiota

     

    Axis 3 - Modulation of the intestinal microbiota using pre- and pro-biotics approaches

    While our research is mainly focusing on detrimental impacts of the microbiota, our expertise in this field of research, our data-set of identified detrimental bacteria and metabolites, as well as the numerous animal models available in the laboratory lead us to work on the development of tools aiming to beneficially alter the intestinal microbiota.

    • Among other approaches, we are:
    • using dietary factor to modulate the microbiota and prevent its deleterious effects
    • using probiotics to beneficially modulates the host/microbiota relationship
    • using approaches to in vivo modulate bacterial gene expression in order protect against intestinal inflammation and neuro-inflammation.

     

    Main Publications

    Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection. Shi Z, Zou J, Zhang Z, Zhao X, Noriega J, Zhang B, Zhao C, Ingle H, Bittinger K, Mattei LM, Pruijssers AJ, Plemper RK, Nice TJ, Baldridge MT, Dermody TS, Chassaing B, Gewirtz AT. Cell. 2019 Oct 17;179(3):644-658.e13. doi: 10.1016/j.cell.2019.09.028. Epub 2019 Oct 10.

    Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD Jr, Zhang L, Wang WB, Hao S, Flythe MD, Gonzalez DJ, Cani PD, Conejo-Garcia JR, Xiong N, Kennett MJ, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M. Cell. 2018 Oct 18;175(3):679-694.e22. doi: 10.1016/j.cell.2018.09.004.

    Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition. Fulde M, Sommer F, Chassaing B, van Vorst K, Dupont A, Hensel M, Basic M, Klopfleisch R, Rosenstiel P, Bleich A, Bäckhed F, Gewirtz AT, Hornef MW. Nature. 2018 Aug;560(7719):489-493. doi: 10.1038/s41586-018-0395-5.

    Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Gut. 2017 Aug;66(8):1414-1427. doi: 10.1136/gutjnl-2016-313099. Epub 2017 Mar 21.

    Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans. Chassaing B, Raja SM, Lewis JD, Srinivasan S, Gewirtz AT. Cell Mol Gastroenterol Hepatol. 2017 Apr 13;4(2):205-221. doi: 10.1016/j.jcmgh.2017.04.001. eCollection 2017 Sep.

    Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis. Viennois E, Merlin D, Gewirtz AT, Chassaing B. Cancer Res. 2017 Jan 1;77(1):27-40. doi: 10.1158/0008-5472.CAN-16-1359. Epub 2016 Nov 7.

    Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT. Nature. 2015 Mar 5;519(7541):92-6. doi: 10.1038/nature14232.

     

    Team’s news

    2019 – 1 single bacterium protecting from viral infection? One more example that bacteria are my friends ! Check it out here 

    2019 – Welcome to Sabrine Naimi, post-doctorate fellow in the laboratory

    2019 – Welcome to Hanh Tong, Assistant Engineer in the laboratory.

    2019 – Our research was part of a 1h documentary on the microbiota !  

    2019 – It’s the beginning of our ERC Starting grant on mucus invaders !

     

    Financial supports