Thus, c‐Kit mutant animals can be used to investigate the function of ICC and GI musculature.[17] Here, with c‐Kit receptor dysfunction‐based ICC‐deficient murine model (Kitwsh/wsh) and chemical‐induced murine model with decreased motility, together with clinical samples, we demonstrate that decreased GI motility might contribute to colitis development through modulating gut microbial composition (especially the abundance of Lactobacillus and Akkermansia muciniphila); and inducing linoleic acid accumulation which resulted in inhibited Treg cell differentiation in a macrophage‐dependent way. This evidence concerns the gene KIT and intrahepatic cholangiocarcinoma.