Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner

Highlights: • Intestinal barrier and NLRC3 expression are impaired in diabetic mice. • NLRC3 ameliorates tight junctions in colonic epithelial cell. • NLRC3 up-regulates ZO-1 and occludin expression via TRAF6 pathway. • Butyrate improves NLRC3 expression by activating GPR43. • Butyrate ameliorates the intestinal epithelial tight junctions in db/db mice. Intestinal barrier dysfunctions are related to dysbacteriosis and chronic gut inflammation in type 2 diabetes. Although there is emerging evidence that the chronic gut inflammatory response is stimulated by nucleotide-binding oligomerization domain-like receptors (NLRs), the relationship and precise mechanism between NLRC3 and the colonic epithelial barrier remains largely elusive.