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Active thrombin produced by the intestinal epithelium controls mucosal biofilms

Author

Listed:
  • Jean-Paul Motta

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Alexandre Denadai-Souza

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • David Sagnat

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Laura Guiraud

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Anissa Edir

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Chrystelle Bonnart

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Mireille Sebbag

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Perrine Rousset

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Ariane Lapeyre

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Carine Seguy

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Noa Mathurine-Thomas

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Heather J. Galipeau

    (McMaster University)

  • Delphine Bonnet

    (Department of Internal Medicine and Digestive Diseases)

  • Laurent Alric

    (Department of Internal Medicine and Digestive Diseases)

  • Andre G. Buret

    (University of Calgary)

  • John L. Wallace

    (University of Calgary Cumming School of Medicine)

  • Antoine Dufour

    (University of Calgary Cumming School of Medicine)

  • Elena F. Verdu

    (McMaster University)

  • Morley D. Hollenberg

    (University of Calgary Cumming School of Medicine)

  • Eric Oswald

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Matteo Serino

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Celine Deraison

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039)

  • Nathalie Vergnolle

    (IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, U1220, CHU Purpan, CS60039
    University of Calgary Cumming School of Medicine)

Abstract

Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.

Suggested Citation

  • Jean-Paul Motta & Alexandre Denadai-Souza & David Sagnat & Laura Guiraud & Anissa Edir & Chrystelle Bonnart & Mireille Sebbag & Perrine Rousset & Ariane Lapeyre & Carine Seguy & Noa Mathurine-Thomas &, 2019. "Active thrombin produced by the intestinal epithelium controls mucosal biofilms," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11140-w
    DOI: 10.1038/s41467-019-11140-w
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