Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN-Induced Bladder Cancer
Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN-Induced Bladder Cancer
复制标题
萝卜硫素使 BBN 诱导的膀胱癌小鼠的肠道菌群正常化并增强肠道屏障
DOI：
10.1002/mnfr.201800427
复制
发表时间：
2018-12-01
影响因子：
5.2
通讯作者：
Shan, Yujuan
中科院分区：
文献类型：
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作者：
He, Canxia;Huang, Lei;Shan, Yujuan
研究范围肠道菌群失调、炎症和肠道屏障缺陷在肿瘤发生中起重要作用。萝卜硫素（SFN）是一种在十字花科蔬菜中发现的异硫氰酸酯，已被证明对抑制癌症非常有效。本研究的目的是研究肠道微生物群在SFN抑制BBN诱导的膀胱癌中的潜在作用。方法和结果用N-丁基-N-（4-羟丁基）-亚硝胺诱导雄性C57 BL/6小鼠膀胱癌，有或无SFN持续23周。SFN改善了膀胱癌的组织学变化特征，导致粘膜下毛细血管减少。SFN使BBN诱导的膀胱癌小鼠的肠道微生物群生态失调正常化，脆弱拟杆菌和梭菌簇I显著增加。SFN还增加小鼠结肠中的丁酸水平，并通过上调紧密连接蛋白和GLP 2的表达来修复结肠和盲肠粘膜上皮的损伤。SFN能显著降低膀胱癌小鼠细胞因子IL-6和分泌型免疫球蛋白A的释放。结论SFN可能通过恢复肠道菌群组成、修复肠道屏障的生理性破坏、减轻炎症反应和免疫应答，从而起到预防化学性膀胱癌的作用。
Scope Gut microbiota imbalance, inflammation, and gut barrier deficiency play an important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has been proven to be highly effective in inhibiting cancer. The objective of this study is to investigate the potential roles of the gut microbiota in the inhibition of BBN-induced bladder cancer by SFN. Methods and Results N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates the histological changes characteristic of bladder cancer, resulting in fewer submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN-induced bladder cancer with a significant increase in Bacteroides fragilis and Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon, and repairs the injury to the mucosal epithelium of the colon and cecum through the upregulation of the expression of tight junction proteins and GLP2. SFN greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A in the mice with bladder cancer. Conclusion These results suggest that SFN protects against chemical-induced bladder cancer through normalizing the composition of gut microbiota and repairing the physiological destruction of the gut barrier, as well as decreasing inflammation and the immune response.