113
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles. Distortion of this balanced AMP landscape by inflammasome deficiency drives dysbiosis development. Upon fecal transfer, colitis-inducing microbiota hijacks this microenvironment-orchestrating machinery through metabolite-mediated inflammasome suppression, leading to distorted AMP balance favoring its preferential colonization. Restoration of the metabolite-inflammasome-AMP axis reinstates a normal microbiota and ameliorates colitis. Together, we identify microbial modulators of the NLRP6 inflammasome and highlight mechanisms by which microbiome-host interactions cooperatively drive microbial community stability through metabolite-mediated innate immune modulation. Therefore, targeted ‘postbiotic’ metabolomic intervention may restore a normal microenvironment, as treatment or prevention of dysbiosis-driven diseases.

          Graphical Abstract

          Related collections

          Author and article information

          Journal
          0413066
          2830
          Cell
          Cell
          Cell
          0092-8674
          1097-4172
          21 October 2017
          03 December 2015
          02 November 2017
          : 163
          : 6
          : 1428-1443
          Affiliations
          [1 ]Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
          [2 ]Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel
          [3 ]Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
          [4 ]Ben Gurion University of the Negev, Beer Sheva 8410501, Israel
          [5 ]The Grand Israel National Center for Personalized Medicine (G-INCPM), Weizmann Institute of Science, Rehovot 76100, Israel
          [6 ]Institute of Innate Immunity, University of Bonn, Bonn 53127, Germany
          [7 ]Department of Medicine, University of Massachusetts, Worcester, MA 01605, USA
          [8 ]Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel
          [9 ]Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
          [10 ]Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel
          [11 ]Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
          [12 ]Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
          Author notes
          [# ]Correspondence to: Eran Segal, Ph.D., Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel, eran.segal@ 123456weizmann.ac.il . Eran Elinav, M.D., Ph.D. Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel, eran.elinav@ 123456weizmann.ac.il
          [*]

          These first authors contributed equally to this work

          [$]

          These corresponding authors contributed equally to this work

          Article
          PMC5665753 PMC5665753 5665753 nihpa909272
          10.1016/j.cell.2015.10.048
          5665753
          26638072
          8458e3e1-b5a5-4be5-9a39-01025781d2cb
          History
          Categories
          Article

          Inflammasome,anti-microbial peptides,microbiota,metabolites

          Comments

          Comment on this article