High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis
High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis
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高脂肪饮食通过扰乱粘膜树突状细胞稳态加剧硫酸右旋糖酐钠诱导的结肠炎
DOI：
10.1016/j.intimp.2016.08.018
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发表时间：
2016-11-01
影响因子：
5.6
通讯作者：
Xia, Sheng
中科院分区：
文献类型：
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作者：
Cheng, Lu;Jin, Huimin;Xia, Sheng
流行病学研究表明，富含脂肪的西方饮食是炎症性肠病(IBD)高发的原因之一。此外，积累的数据表明，脂肪饮食因素可能促进了共生菌群组成和代谢的变化。但是，高脂肪饮食在肠道炎症中的确切机制还没有得到很好的证明。在本研究中，我们发现高脂饮食(HFD)促进了葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎的炎症反应，并加重了疾病的严重程度。与低脂饮食(LFD)/DSS组相比，HFD/DSS组小鼠结肠长度较短，上皮细胞丢失和腺泡破坏较多，Gr-1(+)髓系炎症细胞在结肠内的浸润较多。有趣的是，这种HFD介导的炎症伴随着造血调控的紊乱，在结肠和脾中检测到更多的造血干/祖细胞。我们进一步分析了HFD和DSS治疗对LFD小鼠粘膜DC亚群的影响，发现DSS治疗LFD小鼠主要是显著增加固有层(LP)中CD11c(+)CD103(-)CD11b(+)DC的百分比。而在HFD/DSS小鼠中，HFD预治疗不仅增加了结肠炎小鼠LP和肠系膜淋巴结中CD11c(+)CD103(-)CD11b(+)DC的百分率，而且降低了CD11c(+)CD103(+)CD11b(+)的百分率。HFD/DSS小鼠粘膜树突状细胞的这种失衡可能依赖于丁酸和维甲酸水平的降低。因此，本研究证实了HFD对肠道微环境的影响，并进一步揭示了HFD在DSS诱导的结肠炎发病中的潜在作用。(C)2016爱思唯尔B.V.保留所有权利。
Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1(+) myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c(+)CD103(-) CD11b(+) DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c(+) CD103(-) CD11b(+) DCs, but also decreased CD11c(+) CD103(+) CD11 b(+) in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/ DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis. (C) 2016 Elsevier B.V. All rights reserved.