Dietary Quercetin Protects Against Dextran Sodium Sulfate (DSS)- induced Colitis Mice by Restoring Intestinal Barrier, Reducting Oxidative Stress and Inflammation via Modulating Gut Microbiota

AbstractBackgroundInflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorders of the gastrointestinal tract, and currently the treatment options of IBD remain limited due to its complex pathogenesis. Quercetin (QUE), one of the representative flavonoids with various bioactivities, has many beneficial effects on gut health. However, little is known of its function on colitis. In this study, the protective effects and underlying mechanisms of QUE on colitis were investigated using dextran sulfate sodium (DSS)-induced mice by using 16S rDNA sequencing, immunofluorescence histochemistry, enzyme-linked immunoassay, respectively.ResultOur datas revealed that QUE administration by oral gavage not only ameliorates the symptoms and histopathological change of colitis, but also increases the concentration of mucin2, numbers of goblet cells and the expression of tight junction proteins, including ZO-1, Occludin, and Claudin-1. In addition, we also found that macrophage in colon were skewed to M1 macrophage polarization by DSS treatment, but QUE treatment markedly promoted M2 polarization in mice colon, while the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) were also changed, and received after QUE treatment. In addition, Immunofluorescence results also revealed that QUE upregulated the Nrf2/HO-1 signaling pathway, while the level of oxidative-stress enzymes (superoxide dismutase, glutathione, and catalase) were also reversed by QUE treatment. Furthermore, 16S rDNA sequencing revealed that QUE treatment partially restored the alterations in the gut microbiota in colitis mice, mainly by increasing the abundance of potentially beneficial bacteria (such as Odoribacter) whereas decreasing the abundance of potentially harmful bacteria (such as Bacteroidaceae and Bacteroides).ConclusionQUE had the capacity to treat colitis by maintaining the mucosal barrier, modulating inflammation, decreasing oxidation stress, and reverting gut microbiota changes. This research provides an ideal, healthful, and sustainable approach for IBD treatment.