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

• Published in: Cell reports (Cambridge) Vol. 19; no. 4; pp. 733 - 745
• Main Authors: Seregin, Sergey S., Golovchenko, Natasha, Schaf, Bryan, Chen, Jiachen, Pudlo, Nicholas A., Mitchell, Jonathan, Baxter, Nielson T., Zhao, Lili, Schloss, Patrick D., Martens, Eric C., Eaton, Kathryn A., Chen, Grace Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2017; Elsevier
• Subjects: Akkermansia; Animals; Bacteroides - genetics; Bacteroides - physiology; colitis; Colitis - etiology; Colitis - microbiology; Colitis - pathology; Colon - microbiology; Colon - pathology; Disease Susceptibility; DNA, Bacterial - chemistry; DNA, Bacterial - isolation & purification; DNA, Bacterial - metabolism; dysbiosis; Female; Hyperplasia - etiology; Hyperplasia - pathology; IL-10; inflammation; Inflammation - etiology; Inflammation - pathology; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-18 - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; intestine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; NLRP6; NLRs; pathobiont; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Sequence Analysis, DNA; Verrucomicrobia - genetics; Verrucomicrobia - physiology; Microbiota; colitis; intestine; NLRP6; pathobiont; inflammation; Akkermansia; NLRs; IL-10; dysbiosis
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.03.080

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. [Display omitted] •NLRP6 deficiency promotes colitis in Il10−/− mice•NLRP6 controls colonization of A. muciniphila in an IL-18-dependent manner•Akkermansia muciniphila is sufficient to induce colitis in germ-free Il10−/− mice NLRP6 is important for maintaining intestinal homeostasis. Seregin et al. demonstrate that NLRP6 limits the colonization of mucolytic A. muciniphila, which is sufficient to induce colitis in specific-pathogen-free and germ-free Il10−/− mice. Resistance to A. muciniphila colonization by NLRP6 is mediated by IL-18.