NLRP6 inflammasome is a regulator of colonic microbial ecology and risk for colitis

By Eran Elinav, T. Strowig, A. Kau, Jorge Henao-Mejia, Christoph A. Thaiss, C. Booth, D. Peaper, J. Bertin, S. Eisenbarth, Jeffrey I. Gordon and 1 more. Cell, 2011

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Inflammasomes are multi-protein complexes that function as sensors of endogenous or exogenous damage-associated molecular patterns. Here we show that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7. NLRP6 inflammasome-deficient mice were characterized by spontaneous intestinal hyperplasia, inflammatory cell recruitment, and exacerbation of chemical colitis induced by exposure to dextran sodium sulfate (DSS). Cross-fostering and cohousing experiments revealed that the colitogenic activity of this microbiota is transferable to neonatal or adult wild-type mice, leading to exacerbation of DSS colitis via induction of CCL5. Antibiotic treatment and electron microscopy studies further supported the role of Prevotellaceae as a key representative of this microbiota-associated phenotype. Altogether, perturbations in this inflammasome pathway, including NLRP6, ASC, caspase-1 and IL-18 may constitute a predisposing or initiating event in some cases of human IBD.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/035abb56179f5e3952626fe2a0bfb9eebbd9a961

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Citations in the corpus

Interaction between microbiota and immunity in health and disease (2020, background): “The NLRP6 inflammasome has been linked with regulation of microbiome composition and maintenance of intestinal homeostasis.(70) NLRP6 inflammasome signaling is co-modulated by microbiota-derived metabolites, which regulates epithelial IL-18 secretion and AMP expression profiles.”
Inflammasomes and their roles in health and disease. (2012, background): “Interestingly, in one study Nlrp6 deficiency caused marked changes in the composition of intestinal flora characterized by an increased presence of pathogenic Prevotellaceae and TM7 species (Elinav et al. 2011).”
Defining dysbiosis and its influence on host immunity and disease (2014, background): “Dectin-1 is a receptor that recognizes alpha-mannans from the cell wall of yeast, and mice deficient in this receptor are more susceptible to DSS colitis that can be treated with fluconazole, an antifungal drug that does not target bacteria.”
GENETICS AND PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (2016, background): “, DSS) on genetically susceptible hosts (102, 106).”
Decreased Bacterial Diversity Characterizes an Altered Gut Microbiota in Psoriatic Arthritis and Resembles Dysbiosis of Inflammatory Bowel Disease (2015, background): “6 (45) NA NA Joints with active disease, mean (median) count 4.”