The results of eight studies have shown that VHS in IBS may be mediated through the TLR4, TLR4/NF-κB, TLR4/MyD88/NF-κB, TLR4/NF-κB/CBS, HMGB1/TLR4 pathways (12, 13, 35, 37–41). This evidence concerns the gene HMGB1 and irritable bowel syndrome.