NLRP6 Protects Il10−/− Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

Sergey S. Seregin, Natasha Golovchenko, Bryan Schaf, Jiachen Chen, Nicholas A. Pudlo, Jonathan Mitchell, Nielson T. Baxter, Lili Zhao, Patrick D. Schloss, Eric C. Martens, Kathryn A. Eaton, Grace Y. Chen

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

Dysfunction in host immune responses and pathologic alterations in the gut microbiota, referred to as dysbiosis, can both contribute to the development of inflammatory bowel disease (IBD). However, it remains unclear how specific changes in host immunity or the microbiota cause disease. We previously demonstrated that the loss of the innate immune receptor NLRP6 in mice resulted in impaired production of interleukin-18 (IL-18) and increased susceptibility to epithelial-induced injury. Here, we show that NLRP6 is important for suppressing the development of spontaneous colitis in the Il10−/− mice model of IBD and that NLRP6 deficiency results in the enrichment of Akkermansia muciniphila. A. muciniphila was sufficient for promoting intestinal inflammation in both specific-pathogen-free and germ-free Il10−/− mice. Our results demonstrate that A. muciniphila can act as a pathobiont to promote colitis in a genetically susceptible host and that NLRP6 is a key regulator of its abundance.

Original languageEnglish
Pages (from-to)733-745
Number of pages13
JournalCell Reports
Volume19
Issue number4
DOIs
StatePublished - 25 Apr 2017
Externally publishedYes

Keywords

  • Akkermansia
  • IL-10
  • Microbiota
  • NLRP6
  • NLRs
  • colitis
  • dysbiosis
  • inflammation
  • intestine
  • pathobiont

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