Protective Role Of ?-3 PUFAs In DSS-induced Acute Colitis In Mice

BackgroundInflammatory bowel disease(IBD)is a group of chronic inflammatory disorders of the gastrointestinal tract with pathogenesis being uncertified.It comprises two major types,ulcerative colitis(UC)and Crohn's disease(CD).Fish oil is rich in ?-3 polyunsaturated fatty acids(PUFAs).Researches indicate that ?-3 PUFAs plays an important role in immunomodulation.There has been researches indicating the protective and therapeutic role of ?-3 PUFAs in IBD patients and this role may be related to gut microbiota,but little is known on this area.Object To investigate the inhibitory effect of fish oil on dextran sodium sulfate(DSS)-induced acute colitis in mice and its related mechanisms.Method Eight-week-old C57BL/6 mice were given drinking water containing 2.5%DSS for 5 days to establish an acute colitis model.Mice were divided into control group and DSS group,then subdivided into simple control group,fish oil control group,VSL#3 control group,fish oil+VSL#3 control group,simple DSS group,fish oil DSS group,VSL#3 DSS group,fish oil+VSL#3 DSS group.Fish oil custom feed and/or drinking water dissolved with VSL#3 were given from 2 weeks before modeling to before sacrifice.Mouse feces were collected weekly before modeling.The mice were observed and the body weight of the mice was measured daily after modeling.The mice were sacrificed on the 2nd day after the end of DSS.The colon length and pathological inflammation score were evaluated.Colon tissue Caspase-1,GasderminD,IL-1? expression and activation levels were determined by western blotting.The intestinal flora of mice was determined by 16s rRNA sequencing.Results The mortality,weight loss,colon shortening,macroscopic and pathological inflammation scores of the DSS group were significantly higher than those of the control group.Irn the fish oil DSS group,VSL#3 DSS group and fish oil+VSL#3 DSS group,the colonic inflammation was significantly lower than that of the simple DSS group,the weight loss and pathological inflammation score was significantly reduced,and the mortality was also decreased.There was no significant difference on colon shortening.The fish oil DSS group has significantly lower pathological inflammation score than the VSL#3 DSS group,and the weight loss was decreased,too.16s rRNA analysis of feces showed that VSL#3 had no significant effect on the structure of fecal flora,while fish oil increased the diversity of intestinal flora,which increased the abundance of Firmicutes and decreased the abundance of Bacteroidetes.Compared with the control group,Caspase-1 and IL-1? were not activated and GasderminD was significantly activated in DSS group.The activation of GasderminD in the fish oil DSS group and the fish oil+VSL#3 DSS group was significantly lower than that of the simple DSS group.VSL#3 DSS group showed a lowering trend on GasderminD activation than simple DSS group.The fish oil DSS group showed a lowering trend than the VSL#3 DSS group on GasderminD activation.Conclusion Fish oil can inhibit DSS-induced acute colitis in mice,maintain intestinal flora diversity and change the structure of the flora,and inhibit GasderminD-mediated pyroptosis may be related mechanisms.