Abstract: Objective To investigate the role and mechanism of sodium butyrate in the treatment of irritable bowel syndrome(IBS). Methods A total of 49 participants comprised of 27 diarrhea-dominant IBS(IBS-D)patients and 22 controls were included. The protein expression of interleukin-1 receptor-associated kinase 1(IRAK1)in the colonic epithelium was detected with immunohistochemistry staining. The relationship between the IRAK1 protein expression and abdominal pain scores was analyzed with Spearman correlation analysis. After the animal models of IBS were established by 2,4,6-trinitrobenzene sulphonic acid enema, they were treated with sodium butyrate enema. The visceral hypersensitivity was observed using colorectal distension. The IRAK1 expression was determined with enzyme linked immunosorbent assay(ELISA). The relationship between IRAK1 expression and visceral pain threshold was analyzed with Spearman correlation analysis. After the HT-29 cell lines were treated with IL-33 and sodium butyrate, the IRAK1 protein expression was detected with Western blotting. Results Patients with IBS-D showed a higher expression of IRAK1 in colonic epithelium than the controls and IRAK1 expression was positively correlated with abdominal pain severity scores(r=0.676, P<0.001)and frequency scores(r=0.725, P<0.001). IBS animal models treated with sodium butyrate enema exhibited a lower expression of IRAK1 in the colon tissues and a higher visceral pain threshold. The IRAK1 protein expression was negatively correlated with pain threshold(r=-0.655, P<0.001). IL-33 stimulation could upregulate the protein expression of IRAK1 in HT-29 cell lines, while sodium butyrate pretreatment could diminish the effect. Conclusion Sodium butyrate may ameliorate visceral hypersensitivity in irritable bowel syndrome by down-regulating the protein expression of IRAK1.

Key words: Sodium butyrate, Interleukin-1 receptor-associated kinase 1, Irritable bowel syndrome, Visceral hypersensitivity