Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway

Abstract Background and aim Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. Methods C57BL/6 mice were employed and divided into three groups – control group (n = 8), autoimmune hepatitis group (n = 12) and autoimmune hepatitis with treatment of sodium butyrate group (n = 12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. Results The findings revealed that S100/Freund’s complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines – interleukin-6 and tumor necrosis factor-a. Conclusions Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund’s complete adjuvant induced autoimmune hepatitis.