Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction
Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction
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DOI：
10.1152/ajpendo.00187.2017
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发表时间：
2018-05-01
影响因子：
5.1
通讯作者：
Gentile, Christopher L.
中科院分区：
文献类型：
--
作者：
Battson, Micah L.;Lee, Dustin M.;Gentile, Christopher L.
血管功能障碍是心血管疾病发展的关键临床前步骤。我们研究了肠道微生物群在肥胖相关血管功能障碍发展中的作用。雄性C57BL/6J小鼠被喂食标准饮食（SD） （n = 12）或西方饮食（WD） （n = 24） 5个月，之后WD小鼠被随机分配接受未补充的饮用水或含有广谱抗生素鸡尾酒的水（WD + Abx） （n = 12/组）2个月。WD 7个月导致肠道失调，动脉僵硬度增加（SD 412.0 +/- 6.0 vs WD 458.3 +/- 9.0 cm/s）。P < 0.05)和内皮功能障碍（最大舒张度降低28%）。P < 0.05)， l - name抑制的舒张降低。血管功能障碍伴循环lps结合蛋白（LBP） （SD值5.26 +/- 0.23 vs WD值11 +/- 0.86 mu g/ml, P < 0.05）和白细胞介素-6 (IL-6) （SD值3.27 +/- 0.25 vs WD值7.09 +/- 1.07 mu g/ml, P < 0.05）、主动脉磷酸化核因子- kb （P - nf - kb）表达（P < 0.05）和血管周围脂肪NADPH氧化酶亚基p67phox表达（P < 0.05）。血管功能的损伤与双歧杆菌的减少有关。抗生素治疗成功地消除了肠道微生物群，逆转了wd诱导的动脉僵硬和内皮功能障碍。这些改善伴随着腰痛的显著减少。IL-6， p-NF-KB和晚期糖基化终产物（AGEs），并且独立于体重和葡萄糖耐量的变化。这些结果表明，肠道生态失调有助于wd诱导的血管功能障碍的发展，并确定肠道微生物群作为肥胖相关血管异常的新治疗靶点。
Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesityrelated vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) (n = 12) or Western diet (WD) (n = 24) for 5 mo. after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) (n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 +/- 6.0 vs. WD 458.3 +/- 9.0 cm/s. P < 0.05) and endothelial dysfunction (28% decrease in max dilation. P < 0.05), and reduced L-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 +/- 0.23 vs. WD 11 +/- 0.86 mu g/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 +/- 0.25 vs. WD 7.09 +/- 1.07 mu g/ml, P < 0.05): aortic expression of phosphorylated nuclear factor-kB (p-NF-KB) (P < 0.05): and perivascular adipose expression of NADPH oxidase subunit p67phox (P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP. IL-6, p-NF-KB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.