The NLR protein NLRP6 does not impact gut microbiota composition

NLRP6 is a Nod-like receptor expressed in the intestinal epithelium. Previous studies reported a protective role for NLRP6 against intestinal injury and colitis-associated carcinogenesis via regulation and establishment of a "healthy" microbiota. However, none of these results were obtained using littermate animals, leaving the possibility that the pro-colitogenic microbiota phenotype associated with knockout mice was stochastically acquired and genotype-independent. Here, we analyzed the microbiota at three intestinal locations from Nlrp6-/- and wild type (WT) littermates, either co- caged or individually caged after weaning. Our results demonstrate that Nlrp6 does not significantly impact intestinal microbiota at homeostasis, and confirm a previously reported sex-biased microbial community structure. Moreover, WT and Nlrp6-/- littermate mice displayed comparable sensitivity to DSS-induced colitis, although we noted a moderately increased sensitivity of knockout female mice. Our results clarify the role of NLRP6 in microbiota and colitis control, and highlight the importance of analyzing littermate animals in such studies.