Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.
Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.
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DOI：
10.1136/gutjnl-2016-313316
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发表时间：
2018-03
期刊：
影响因子：
24.5
通讯作者：
Delzenne NM
中科院分区：
文献类型：
--
作者：
Catry E;Bindels LB;Tailleux A;Lestavel S;Neyrinck AM;Goossens JF;Lobysheva I;Plovier H;Essaghir A;Demoulin JB;Bouzin C;Pachikian BD;Cani PD;Staels B;Dessy C;Delzenne NM
在将脂肪变性和内皮功能障碍联系起来的原始小鼠模型中，研究益生元对内皮功能障碍（心血管疾病的早期关键标志物）的有益作用。我们研究了在载脂蛋白 E 敲除 (Apoe−/−) 小鼠中观察到的肠道微生物群对血管功能障碍的影响，这些小鼠喂食 n-3 多不饱和脂肪酸 (PUFA) 耗尽的饮食 12 周，并在最后 15 天补充或不补充菊粉型果聚糖 (ITF)。分离肠系膜和颈动脉以评估离体内皮依赖性松弛。还评估了盲肠微生物群组成（16S rRNA 基因的 Illumina 测序）和参与血管功能控制的关键途径/介质，包括胆汁酸 (BA) 分析、肠道和肝脏关键基因表达、一氧化氮和肠道激素的产生。 ITF 补充剂通过激活一氧化氮 (NO) 合酶/NO 途径，完全逆转 n-3 PUFA 耗尽的 Apoe−/− 小鼠肠系膜和颈动脉的内皮功能障碍。益生元治疗引起的肠道微生物群变化包括产生 NO 的细菌增加、Akkermansia 丰度补充以及参与二次 BA 合成的细菌类群丰度减少。肠道和肝脏基因表达的变化也发生在 ITF 上，表明胰高血糖素样肽 1 的产生和 BA 周转增加是内皮功能保存的驱动因素。我们首次证明 ITF 可以改善内皮功能障碍，这意味着肠道微生物群和关键肠道肽的短期适应。如果在人体中得到证实，益生元可以作为预防代谢紊乱相关心血管疾病的新方法。
To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe−/−) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed. ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe−/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation. We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.
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影响因子：
6.4
作者：
Delzenne NM;Neyrinck AM;Cani PD
通讯作者：
Cani PD
DOI：
10.1038/ismej.2014.45
发表时间：
2014-10
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
6.9
作者：
Bigornia, Sherman J.;Mott, Melanie M.;Gokce, Noyan
通讯作者：
Gokce, Noyan
影响因子：
37.8
作者：
Juonala, M;Viikari, JSA;Raitakari, OT
通讯作者：
Raitakari, OT