P036 Microbiota Metabolite Butyrate Attenuates Intestinal Inflammation Through Autophagy Activation

Abstract

Abstract Background Alteration of the microbiota metabolite short chain fatty acids (SCFAs) may contribute to the development of inflammatory bowel disease (IBD). Butyrate, one of the SCFAs produced by bacteria, is known to be beneficial in attenuating intestinal inflammation. However, the mechanisms underlying anti-inflammatory effects of butyrate have not yet been entirely investigated. Methods In vivo, wild-type C57BL/6J mice were given a gavage of sodium butyrate (SB) (0.12g/ml) for 5 days. The mice were then administered 2% dextran sodium sulfate to induce experimental colitis models. Fecal microbiota was analysed by 16S rDNA sequencing. In vitro, HCT116 cell line was used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response. The levels of inflammatory cytokines, intestinal tight junction and autophagy were detected by western blotting and quantitative polymerase chain reaction. Results We observed that SB treatment significantly attenuated colitis in rodent models with reduced tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β expression, and tended to restore intestinal barrier dysfunction. Mechanically, we identified that the inclusion of SB enhanced protein level of Atg16l1, which indicated enhanced autophagy function. In vitro cell experiments also proved that mRNA levels of IL-6 and TNF-α were decreased, while autophagy-related Beclin was enhanced. Furthermore, our results revealed a distinct alteration mediated by butyrate in the gut microbiota by restored ratio of Firmicutes/Bacteroides, increasing Erysipelotrichaceae and reduced Desulfovibrio abundance. Conclusion This study provides the first data demonstrating that butyrate supplementation attenuates intestinal inflammation probably via promoting autophagy and regulating intestinal microbiota. Our findings provide new insights into butyrate-mediated remission of IBD and butyrate as a potential modulator for autophagy to prevent and treat IBD.