Moreover, significant delay in GI motility has been observed in mice with mutated TLR4 and in TLR4 knock-out mice [144], while increased TLR4 expression has been reported in colonic biopsies of patients with IBS-D, an increase that reached by 15-fold in patients with inflammatory bowel disease (IBD), and was shown to be upregulated by LPS and flagellin [145,146]. Here, TLR4 is linked to inflammatory bowel disease.