High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production.
High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production.
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DOI：
10.1186/s40168-018-0433-4
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发表时间：
2018-03-22
期刊：
影响因子：
15.5
通讯作者：
Bercik P
中科院分区：
文献类型：
--
作者：
Miranda PM;De Palma G;Serkis V;Lu J;Louis-Auguste MP;McCarville JL;Verdu EF;Collins SM;Bercik P
卫生和饮食习惯的改变，包括增加食用高脂肪、单糖和盐的食物，这些食物已知会影响肠道微生物群的组成和功能，这可能解释慢性炎症性疾病患病率的增加。在小鼠模型中，高盐消耗已显示通过p38/MAPK信号通路使自身免疫性脑脊髓炎和结肠炎恶化。然而，高盐饮食（HSD）对肠道微生物群和肠道免疫稳态的影响，以及它们在确定肠道炎症刺激的脆弱性中的作用尚不清楚。在这里，我们研究了HSD诱导的肠道微生物群改变对小鼠实验性结肠炎严重程度的作用。与对照饮食相比，HSD改变了粪便微生物群的组成和功能，减少了乳杆菌属的相对丰度和丁酸盐的产生。此外，HSD通过增强促炎基因如Rac 1、Map 2k 1、Map 2k 6、Atf 2的表达，同时抑制许多细胞因子和趋化因子基因如Ccl 3、Ccl 4、Cxcl 2、Cxcr 4、Ccr 7，影响结肠粘膜免疫，并且在较小程度上影响小肠粘膜免疫。与对照饮食的小鼠相比，用HSD喂养的常规饲养小鼠出现了更严重的DSS-（葡聚糖硫酸钠）和DNBS-（二硝基苯磺酸）诱导的结肠炎，而无菌小鼠中不存在这种效应。转移到无菌小鼠的实验表明，与HSD-associated微生物群的概况是严重依赖于持续暴露于膳食盐。我们的研究结果表明，由HSD引起的结肠炎的恶化与乳酸杆菌属的减少和保护性短链脂肪酸的产生以及宿主免疫状态的变化有关。我们假设这些变化改变了肠道免疫稳态，并导致对炎症损伤的脆弱性增加。本文的在线版本（10.1186/s40168-018-0433-4）包含补充材料，可供授权用户使用。
Changes in hygiene and dietary habits, including increased consumption of foods high in fat, simple sugars, and salt that are known to impact the composition and function of the intestinal microbiota, may explain the increase in prevalence of chronic inflammatory diseases. High salt consumption has been shown to worsen autoimmune encephalomyelitis and colitis in mouse models through p38/MAPK signaling pathway. However, the effect of high salt diet (HSD) on gut microbiota and on intestinal immune homeostasis, and their roles in determining vulnerability to intestinal inflammatory stimuli are unknown. Here, we investigate the role of gut microbiota alterations induced by HSD on the severity of murine experimental colitis. Compared to control diet, HSD altered fecal microbiota composition and function, reducing Lactobacillus sp. relative abundance and butyrate production. Moreover, HSD affected the colonic, and to a lesser extent small intestine mucosal immunity by enhancing the expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while suppressing many cytokine and chemokine genes, such as Ccl3, Ccl4, Cxcl2, Cxcr4, Ccr7. Conventionally raised mice fed with HSD developed more severe DSS- (dextran sodium sulfate) and DNBS- (dinitrobenzene sulfonic acid) induced colitis compared to mice on control diet, and this effect was absent in germ-free mice. Transfer experiments into germ-free mice indicated that the HSD-associated microbiota profile is critically dependent on continued exposure to dietary salt. Our results indicate that the exacerbation of colitis induced by HSD is associated with reduction in Lactobacillus sp. and protective short-chain fatty acid production, as well as changes in host immune status. We hypothesize that these changes alter gut immune homeostasis and lead to increased vulnerability to inflammatory insults. The online version of this article (10.1186/s40168-018-0433-4) contains supplementary material, which is available to authorized users.
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影响因子：
30.3
作者：
Devlin AS;Marcobal A;Dodd D;Nayfach S;Plummer N;Meyer T;Pollard KS;Sonnenburg JL;Fischbach MA
通讯作者：
Fischbach MA
影响因子：
30.3
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通讯作者：
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影响因子：
64.8
作者：
Kleinewietfeld, Markus;Manzel, Arndt;Titze, Jens;Kvakan, Heda;Yosef, Nir;Linker, Ralf A.;Muller, Dominik N.;Hafler, David A.
通讯作者：
Hafler, David A.