| Literature DB >> 26638072 |
Maayan Levy1, Christoph A Thaiss1, David Zeevi2, Lenka Dohnalová1, Gili Zilberman-Schapira1, Jemal Ali Mahdi3, Eyal David1, Alon Savidor4, Tal Korem2, Yonatan Herzig1, Meirav Pevsner-Fischer1, Hagit Shapiro1, Anette Christ5, Alon Harmelin6, Zamir Halpern7, Eicke Latz5, Richard A Flavell8, Ido Amit1, Eran Segal9, Eran Elinav10.
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.Entities:
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Year: 2015 PMID： 26638072 PMCID： PMC5665753 DOI： 10.1016/j.cell.2015.10.048
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582