A dietary flavone confers communicable protection against colitis through NLRP6 signaling independently of inflammasome activation

Katarina Radulovic (1, 2) , Sylvain Normand (1) , Ateequr Rehman (3) , Anne Delanoye-Crespin (1) , J Chatagnon (1) , Myriam Delacre (1) , Nadine Waldschmitt (1) , Lionel F Poulin (1) , Juan Iovanna (4) , Bernhard Ryffel , Philip Rosenstiel (3) , Mathias Chamaillard (1)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 Department of Biomedicine [Basel]
3 Institute of Clinical Molecular Biology
4 CRCM - Centre de Recherche en Cancérologie de Marseille

Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6. Sequencing of the 16S ribosomal RNA gene revealed a shift in the composition of the gut microbiota in apigenin-treated mice that was not observed in the absence of Nlrp6. Equally important, we find that the antiproliferative effect of apigenin was dominantly transmitted after cohousing, while being compromised in Nlrp6-deficient mice. In contrast, the symptoms of colitis were alleviated upon apigenin administration even in the absence of either caspase-1/11 or Asc. Collectively, these data indicate that apigenin modulated an inflammasome-independent mechanism by which Nlrp6 reprograms the gut microbiota for protecting mice against colitis. Our study highlights a modulation of the Nlrp6 signaling pathway by a prominent constituent of the human diet that may point toward improved ways to treat inflammatory bowel diseases.

Mots clés: inflammasome; flavone; gut microbiota; colitis

Domaines: Sciences du Vivant [q-bio]

Katarina Radulovic, Sylvain Normand, Ateequr Rehman, Anne Delanoye-Crespin, J Chatagnon, et al.. A dietary flavone confers communicable protection against colitis through NLRP6 signaling independently of inflammasome activation: Apigenin regulates bacterial ecology by Nlrp6 signaling. Mucosal Immunology, 2017, 11 (3), pp.811-819. ⟨10.1038/mi.2017.87⟩. ⟨hal-01788846⟩