Gut microbiota, NLR proteins, and intestinal homeostasis

The gastrointestinal tract harbors a highly complex microbial community, which is referred to as gut microbiota. With increasing evidence suggesting that the imbalance of gut microbiota plays a significant role in the pathogenesis of multiple diseases, interactions between the host immune system and the gut microbiota are now attracting emerging interest. Nucleotide-binding and leucine-rich repeat-containing receptors (NLRs) encompass a large number of innate immune sensors and receptors, which mediate the activation of Caspase-1 and the subsequent release of mature interleukin-1β and interleukin-18. Several family members have been found to restrain rather than activate inflammatory cytokines and immune signaling. NLR family members are central regulators of pathogen recognition, host immunity, and inflammation with utmost importance in human diseases. In this review, we focus on the potential roles played by NLRs in controlling and shaping the microbiota community and discuss how the functional axes interconnecting gut microbiota with NLRs impact the modulation of colitis, inflammatory bowel diseases, and colorectal cancer.The authors acknowledge many investigators in the field whose primary data could not be cited in this review because of space limitations. This work was supported by grants from the National Institute of Allergy and Infectious Diseases (grant R01-AI029564), National Institutes of Health (grant R35CA232109), National Institute of Diabetes and Digestive and Kidney Diseases (grant P01-DK094779), and RadCCORE (grant AI067798 to J.P.Y. Ting) and ITCMS T32 (grant 5T32CA009156 to S.A. Gibson). Author contributions: H. Guo wrote the initial draft, prepared and created the figures and tables, and revised the paper. S.A. Gibson wrote the initial draft and prepared and created the figures and Table 2. J.P.Y. Ting provided oversight and leadership responsibility for this paper and edited the manuscript. Disclosures: J.P.Y. Ting reported a patent to University of North Carolina, currently pending, and is the cofounder of GoldCrest Bio, a company that is looking at the role of the microbiota in radiation sickness. H. Guo holds equity shares in GoldCrest Bio. No other disclosures were reported