Abstract：
Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC.
摘要：
炎症性肠病（IBD）涉及慢性炎症，上皮完整性的丧失，和胃肠道微生物群失调，导致结肠癌的发展，称为结肠炎相关结直肠癌（CAC）。在这项研究中,我们评估了corylin在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中的作用。结果表明，corylin可以提高存活率和结肠长度，保持体重，并改善了结肠的炎症反应。然后，我们进一步确定了在氧化偶氮甲烷(AOM)/DSS诱导的CAC小鼠模型上使用Corylin治疗30天后可能的抗肿瘤作用.与炎症相关的生物标志物，结肠组织屏障，巨噬细胞极化(CD11c，CCR7、CD163和CD206)，在AOM/DSS组与Corylin组相比，监测了微生物群失调。Corylin下调促炎细胞因子（TNF-α，IFN-γ，IL-1β,和IL-6)mRNA表达和炎症信号相关标志物(TLR4、MyD88、AP-1、CD11b、和F4/80）。此外,结肠屏障实验显示，粘液层的上皮细胞增殖（Lgr5，CyclinD1和Olfm4）下调，紧密连接蛋白（claudin-1和ZO-1）上调。此外，Firmicutes/Bacteroides比率随Corylin干预而变化，Corylin提高了AOM/DSS小鼠的微生物多样性和群落丰富度。肠道菌群的比较分析表明，拟杆菌，芽孢杆菌,CandidatusSacchiimonas,丹毒病菌，和肠背显著增加，但Firmicutes，Turicibacter,Romboutsia,科林林治疗后，布劳特氏菌减少了。总之,corylin给药通过调节炎症降低结肠炎相关结肠癌的风险，显示出改善癌症的作用，致癌作用，和肠道微生物群的组成变化。因此,Corylin可能是一部小说,潜在的健康保护，抗CAC的天然试剂。
