Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice--role of intestinal permeability and macrophage activation.
Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice--role of intestinal permeability and macrophage activation.
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DOI：
10.1371/journal.pone.0108577
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ghosh S
中科院分区：
文献类型：
--
作者：
Ghosh SS;Bie J;Wang J;Ghosh S
循环脂多糖 (LPS) 与代谢疾病（如 2 型糖尿病和动脉粥样硬化）之间的关联已将焦点从西方饮食引起的肠道微生物群本身的变化转移到肠道细菌衍生产物释放到循环中，作为这些疾病发展背后的慢性炎症状态的可能机制。在生理条件下，完整的肠道屏障可以防止脂多糖的释放，这强调了检查和调节西方饮食对肠道屏障功能的直接影响的重要性。在本研究中，我们评估了两种策略，即选择性肠道净化和补充口服姜黄素，以调节西方饮食（WD）引起的肠道屏障功能变化以及随后的葡萄糖不耐受和动脉粥样硬化的发展。 LDLR−/− 小鼠被喂食 16 周，并在饮用水中接受不可吸收的抗生素（新霉素和多粘菌素）以选择性肠道净化，或每天用姜黄素灌胃。通过 FITC-葡聚糖的体内易位和血浆 LPS 水平评估，WD 显着增加了肠道通透性。选择性肠道净化和补充姜黄素显着减弱了 WD 诱导的血浆 LPS 水平升高（分别为 3.32 vs 1.90 或 1.51 EU/ml），并在多个水平上改善了肠道屏障功能（恢复肠道碱性磷酸酶活性和紧密连接蛋白 ZO-1 和 Claudin-1 的表达）。因此，这两种干预措施均显着降低了 LDLR−/− 小鼠中 WD 诱导的葡萄糖耐受不良和动脉粥样硬化。低水平 LPS (50 ng/ml) 激活巨噬细胞以及脂肪酸加剧巨噬细胞可能是由于肠道屏障功能破坏而导致微量 LPS 释放到循环中诱导这些疾病发生的机制。这些研究不仅确立了肠道屏障功能的重要作用，而且还确定口服补充姜黄素作为改善肠道屏障功能和预防代谢性疾病发展的潜在治疗策略。
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR−/− mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR−/− mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases.
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影响因子：
3.7
作者：
Kiffer-Moreira, Tina;Sheen, Campbell R.;Millan, Jose Luis
通讯作者：
Millan, Jose Luis
影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
DOI：
10.1158/1940-6207.capr-12-0281
发表时间：
2013-02
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Irving GR;Howells LM;Sale S;Kralj-Hans I;Atkin WS;Clark SK;Britton RG;Jones DJ;Scott EN;Berry DP;Hemingway D;Miller AS;Brown K;Gescher AJ;Steward WP
通讯作者：
Steward WP
影响因子：
2.8
作者：
Genth-Zotz, S;von Haehling, S;Anker, SD
通讯作者：
Anker, SD
影响因子：
120.7
作者：
O'Connor, CM;Dunne, MW;Cook, TD
通讯作者：
Cook, TD