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益生元葡萄渣提取物与益生菌sp.的合生元组合降低了脂多糖处理的Caco-2细胞中重要的肠道炎症标志物和深入的信号传导介质。

Synbiotic combination of prebiotic grape pomace extract and probiotic sp. reduced important intestinal inflammatory markers and in-depth signalling mediators in lipopolysaccharide-treated Caco-2 cells.

作者信息

Pistol Gina Cecilia, Marin Daniela Eliza, Dragomir Catalin, Taranu Ionelia

机构信息

Laboratory of Animal Biology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, Balotesti, Romania.

Laboratory of Chemistry and Nutrition Physiology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, Balotesti, Romania.

出版信息

Br J Nutr. 2019 Feb 14;121(3):291-305. doi: 10.1017/S0007114518003410. Epub 2018 Dec 19.

Abstract

Inflammatory bowel diseases (IBD) are a major problem for public health, with an increased incidence and impact on life quality. The effect of pre- and probiotic combination has been less studied in IBD. Using genomic and proteomic array technologies, this study examined the efficacy of a new combination of natural alternatives: prebiotics (grape pomace extract, GP) and probiotics (lactobacilli mixture, Lb mix) on inflammation and intracellular signalling routes in a cellular model of inflammation. Caco-2 cells challenged with lipopolysaccharide (LPS) for 4 h were treated with GP extract (50 μg/ml gallic acid equivalent) and Lb combination (3 × 108 colony-forming units/ml total Lb) for 24 h. The profile expressions of forty key inflammatory markers and twenty-six signalling kinases were analysed. Other markers involved in inflammation were also investigated (NF-κB/RELA, Nrf2, aryl hydrocarbon receptor, Cyp1A1, Cyp1B1); 57·5 and 60 % of investigated genes and proteins, respectively, were down-regulated by the synbiotic combination. Relevant cytokines and chemokines involved in response to microbial infection and inflammation were reduced under the level induced by LPS treatment and toward the unchallenged control. As expected, the reduction effect seems to imply mitogen-activated protein kinase and NF-κB pathway. Most of the signalling molecules activated by LPS were decreased by GP extract and Lb mix. Our study indicates that the synbiotic combination of GP extract and Lactobacillus sp. mixture exerted anti-inflammatory properties, which are able to decrease the majority of inflammatory genes, their proteins and associated signalling markers. Due to protective role of GP compounds on lactobacilli probiotic, this synbiotic combination might serve as a promising adjunctive therapy in intestinal inflammations.

摘要

炎症性肠病(IBD)是一个重大的公共卫生问题,其发病率不断上升,对生活质量产生影响。益生元和益生菌组合在IBD中的作用研究较少。本研究利用基因组和蛋白质组阵列技术,在炎症细胞模型中检测了一种新的天然替代品组合的功效:益生元(葡萄渣提取物,GP)和益生菌(乳酸菌混合物,Lb mix)对炎症和细胞内信号通路的影响。用脂多糖(LPS)刺激4小时的Caco-2细胞用GP提取物(50μg/ml没食子酸当量)和Lb组合(3×108菌落形成单位/ml总Lb)处理24小时。分析了40种关键炎症标志物和26种信号激酶的表达谱。还研究了其他与炎症相关的标志物(NF-κB/RELA、Nrf2、芳烃受体、Cyp1A1、Cyp1B1);合生元组合分别下调了57.5%和60%的研究基因和蛋白质。参与微生物感染和炎症反应的相关细胞因子和趋化因子在LPS处理诱导的水平以下,并向未受刺激的对照水平降低。正如预期的那样,这种降低作用似乎意味着丝裂原活化蛋白激酶和NF-κB途径。LPS激活的大多数信号分子被GP提取物和Lb mix降低。我们的研究表明,GP提取物和乳酸菌混合物的合生元组合具有抗炎特性,能够减少大多数炎症基因、其蛋白质和相关信号标志物。由于GP化合物对乳酸菌益生菌的保护作用,这种合生元组合可能成为肠道炎症中有前景的辅助治疗方法。

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