NLRPs, microbiota, and gut homeostasis: unravelling the connection

Within the NOD-like receptor (NLR) family, there are several NLRP (NLR family, pyrin domain-containing) proteins that are involved in the formation of inflammasomes. These multi-protein complexes are a key part of the network of cellular events required for secretion of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is the best-characterized member of the family and has recently been implicated in gut homeostasis and determining the severity of inflammation in inflammatory bowel disease (IBD) and inflammation-associated colorectal cancer. This led to the discovery that NLRP6 and NLRP12 also contribute to the maintenance of intestinal homeostasis and modulation of the gut microbiota, which in turn influences the intestine and distant organs. In this review, we bring together the latest data on the potential roles of NLRP family members in gut health and disease and identify the most pressing questions that remain to be answered to further our understanding of human diseases including IBD, inflammation-associated cancers, and metabolic syndromes linked with obesity.