Effects of genistein on intestinal short-chain fatty acids in dextran sulfate sodium salt-induced ulcerative colitis mice based on targeted metabolomic analysis
OBJECTIVE To explore the effect of genistein on metabolism of short-chain fatty acids(SCFAs)in mice with ulcerative colitis(UC)induced by dextran sulfate sodium salt(DSS)using targeted metabolomics.METHODS Twenty-seven specific pathogen free(SPF)male Balb/c mice were randomized into 3 groups.No intervention was applied in control group while UC model was constructed by giving DSS drinking water(5％,W/V)in model and treatment groups.After successful model-ing,treatment group received an intragastric injection of genistein(15 mg·kg-1)while model group had the same amount of saline for 7 days.Additionally,disease activity index(DAI)scores were performed.At the end of experiment,pathological observa-tions of colon were made by hematoxylin-eosin(HE)stain and serum levels of interleukin-10(IL-10),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β)and transforming growth factor-beta(TGF-β)were measured by enzyme-linked immunosorbent assay(ELISA).And the level of SCFAs in intestinal contents were performed by gas chromatog-raphy mass spectrometry(GC-MS).RESULTS Pathological examinations revealed genistein could restore mucosal structure significantly and alleviate inflammatory infiltration.Moreover,model group had lower levels of IL-10 and TGF-β and higher lev-els of IL-6,TNF-α and IL-1β than normal group(P＜0.05).There were higher levels of IL-10 and TGF-β and lower levels of IL-6,TNF-α and IL-1β in treatment group as compared with model group(P＜0.05).The findings of targeted metabolomic analysis indicated differences in distance between model and normal groups using orthogonal partial least squares discriminant analysis(OPLSDA).Treatment group approximated normal group.The quantitative data of SCFAs showed a downward trend of acetic acid,butyric acid,and propionic acid and an upward trend of valeric acid in model group as compared with normal group(P＜0.05).Furthermore,as compared with model group,an upward trend was observed in acetic acid,butyric acid and propi-onic acid along with a downward trend in valeric acid(P＜0.05).CONCLUSION Genistein has been shown to exhibit related efficacy through alleviating mucosal barrier injury,mitigating inflammatory infiltration,reducing the levels of pro-inflammatory factors IL-6,TNF-α and IL-1β,increasing the levels of acetic acid,butyric acid and propionic acid in SCFAs and suppressing the levels of valeric acid in UC model.
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