补充半乳糖寡糖可减轻 C57BL/6 小鼠高脂高胆固醇饮食诱导的葡萄糖不耐受和结肠粘蛋白层破坏，并减少 LDLR-/- 小鼠的动脉粥样硬化。

Dietary Supplementation with Galactooligosaccharides Attenuates High-Fat, High-Cholesterol Diet-Induced Glucose Intolerance and Disruption of Colonic Mucin Layer in C57BL/6 Mice and Reduces Atherosclerosis in Ldlr-/- Mice.

机构信息

Department of Internal Medicine, VCU Medical Center, Richmond, VA, USA.

Hunter Homes McGuire VA Medical Center, Richmond, VA, USA.

出版信息

J Nutr. 2020 Feb 1;150(2):285-293. doi: 10.1093/jn/nxz233.

DOI:10.1093/jn/nxz233

PMID:31586202

Abstract

BACKGROUND

A Western-type diet (WD), rich in fat and cholesterol but deficient in fiber, induces development of diabetes and atherosclerosis. Colonic bacteria use the gut's mucous lining as an alternate energy source during periods of fiber deficiency, resulting in intestinal barrier erosion.

OBJECTIVE

We hypothesized that supplementing a WD with galactooligosaccharide (GOS) fiber would attenuate WD-induced mucin layer disruption and attenuate development of metabolic diseases.

METHODS

C57BL/6 mice (both sexes, 8-10 wk of age) were fed a standard rodent diet (TD7012, reference) or a high-fat, high-cholesterol-containing WD (TD88137, 21% fat, 0.15% cholesterol, 19.5% caesin) or a WD supplemented with 5% GOS fiber (TD170432, WD + GOS) for 16 wk. WD-fed mice that were gavaged daily with curcumin (100 mg/kg) served as positive controls. Glucose tolerance, colonic mucin layer, gene expression, and circulating macrophage/neutrophil levels were determined. Hyperlipidemic Ldlr-/- mice (both sexes, 8-10 wk of age) fed a WD with or without GOS supplementation (for 16 wk) were used to assess plasma LPS and atherosclerosis. Effects of dietary supplementation on different parameters were compared for each genotype.

RESULTS

Compared with a WD, glucose tolerance was significantly improved in male C57BL/6 mice fed a WD + GOS (mean ± SEM: AUC = 53.6 ± 43.9 compared with 45.4 ± 33.3 g ⋅ min/dL; P = 0.015). Continuity of colonic mucin layer (MUC-2 expression) was improved in mice receiving GOS supplementation, indicating improved intestinal barrier. GOS supplementation also reduced circulating macrophages (30% decrease) and neutrophils (60% decrease), suggesting diminished systemic inflammation. In Ldlr-/- mice, GOS supplementation significantly reduced plasma LPS concentrations (mean ± SEM: 0.81 ± 0.43 EU/mL compared with 0.32 ± 0.26 EU/mL, P < 0.0001, in females and 0.56 ± 0.24 EU/mL compared with 0.34 ± 0.12 EU/mL, P = 0.036, in males), improved glucose tolerance in male mice, and attenuated atherosclerotic lesion area (mean ± SEM: 54.2% ± 6.19% compared with 43.0% ± 35.12%, P = 0.0006, in females and 54.6% ± 3.99% compared with 43.1% ± 8.11%, P = 0.003, in males).

CONCLUSIONS

GOS fiber supplementation improves intestinal barrier in C57BL/6 and Ldlr-/- mice and significantly attenuates WD-induced metabolic diseases and, therefore, may represent a novel strategy for management of these diseases.

摘要

背景

富含脂肪和胆固醇但缺乏纤维的西方饮食会导致糖尿病和动脉粥样硬化的发生。当纤维缺乏时，结肠细菌会将肠道的黏膜用作替代能量来源，从而导致肠道屏障受损。

目的

我们假设在西方饮食中补充半乳糖寡糖（GOS）纤维可以减轻西方饮食引起的粘蛋白层破坏，并减轻代谢疾病的发展。

方法

将 8-10 周龄的 C57BL/6 雄性和雌性小鼠（雌雄各半）分别喂食标准啮齿动物饮食（TD7012，对照）、高脂肪高胆固醇饮食（TD88137，21%脂肪、0.15%胆固醇、19.5%酪蛋白）或添加 5% GOS 纤维的高脂肪高胆固醇饮食（TD170432，WD+GOS）16 周。每天给予 WD 喂养的小鼠（100mg/kg）姜黄素灌胃作为阳性对照。测定葡萄糖耐量、结肠粘蛋白层、基因表达和循环巨噬细胞/中性粒细胞水平。还使用高脂血症 LDLR-/-小鼠（雌雄各半，8-10 周龄）来评估添加 GOS 前后的血浆 LPS 和动脉粥样硬化情况。比较了不同基因型饮食补充对不同参数的影响。

结果

与 WD 相比，WD+GOS 喂养的雄性 C57BL/6 小鼠的葡萄糖耐量显著改善（平均±SEM：AUC=53.6±43.9 与 45.4±33.3 g ⋅ min/dL 相比；P=0.015）。接受 GOS 补充的小鼠结肠粘蛋白层（MUC-2 表达）连续性得到改善，表明肠道屏障得到改善。GOS 补充还减少了循环中的巨噬细胞（减少 30%）和中性粒细胞（减少 60%），表明全身性炎症减轻。在 LDLR-/- 小鼠中，GOS 补充显著降低了血浆 LPS 浓度（平均±SEM：0.81±0.43 EU/mL 与 0.32±0.26 EU/mL 相比，女性中 P<0.0001，男性中 0.56±0.24 EU/mL 与 0.34±0.12 EU/mL 相比，P=0.036），改善了雄性小鼠的葡萄糖耐量，并减轻了动脉粥样硬化病变面积（平均±SEM：54.2%±6.19% 与 43.0%±35.12% 相比，女性中 P=0.0006，54.6%±3.99% 与 43.1%±8.11% 相比，男性中 P=0.003）。