Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis.
Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis.
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DOI：
10.1371/journal.pone.0055468
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gibson DL
中科院分区：
文献类型：
--
作者：
Ghosh S;DeCoffe D;Brown K;Rajendiran E;Estaki M;Dai C;Yip A;Gibson DL
临床上，过多的ω-6多不饱和脂肪酸和不足的ω-3多不饱和脂肪酸会增加患溃疡性结肠炎的风险。在啮齿动物模型中，不同的研究表明，ω-3多不饱和脂肪酸可以减轻或加重结肠炎。我们假设较高的ω-6：ω-3多不饱和脂肪酸比率会通过微生物-免疫关系增加结肠炎的易感性。为了解决这个问题，我们给断奶后的小鼠喂以富含ω-6PUFA(玉米油)的饲料，并在饲料中添加ω-3PUFA(玉米油+鱼油)，为期5周。我们评估肠道微生物区系，用轮状柠檬酸杆菌诱导结肠炎，并跟踪疾病进展。我们发现ω-6多不饱和脂肪酸富含肠杆菌科细菌、节段性丝状细菌和梭状芽孢杆菌，这些都是已知的诱导炎症的物质。在感染性结肠炎过程中，喂饲ω-6多不饱和脂肪酸的小鼠肠道损伤加重，免疫细胞浸润，前列腺素E_2表达和轮状芽孢杆菌跨肠粘膜移位。在高ω-6多不饱和脂肪酸饮食中添加ω-3多不饱和脂肪酸，逆转了炎症诱导的微生物繁殖，丰富了乳杆菌和双歧杆菌等有益微生物，减少了免疫细胞的渗透，并削弱了感染期间细胞因子/趋化因子的诱导。虽然补充ω-3多不饱和脂肪酸对严重结肠炎有保护作用，但这些小鼠的死亡率与脓毒症相关的血清因子如内毒素结合蛋白、IL-15和肿瘤坏死因子-α有关。这些小鼠还表现出肠道碱性磷酸酶表达减少，并且不能使内毒素去磷酸化。因此，通过不同的多不饱和脂肪酸组成，结肠微生物区系发生了不同的变化，从而改变了对结肠炎的易感性。总体而言，ω-6多不饱和脂肪酸丰富了促炎微生物，加剧了结肠炎；但防止了感染引发的全身炎症。相反，补充ω-3多不饱和脂肪酸逆转了ω-6多不饱和脂肪酸饮食的影响，但削弱了感染诱导的反应，导致败血症。我们的结论是，作为一种抗炎剂，在感染期间补充ω-3多不饱和脂肪酸可能被证明是有害的，因为宿主的炎症反应对生存至关重要。
Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival.
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影响因子：
7.1
作者：
Kris-Etherton, PM;Taylor, DS;Etherton, TD
通讯作者：
Etherton, TD
影响因子：
30.3
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影响因子：
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作者：
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影响因子：
64.5
作者：
Garrett, Wendy S.;Lord, Graham M.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.