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

摘要: BACKGROUND A Western-type diet (WD), rich in fat and cholesterol but deficient fiber, induces development of diabetes atherosclerosis. Colonic bacteria use the gut's mucous lining as an alternate energy source during periods fiber deficiency, resulting intestinal barrier erosion. OBJECTIVE We hypothesized that supplementing a WD with galactooligosaccharide (GOS) would attenuate WD-induced mucin layer disruption metabolic diseases. METHODS C57BL/6 mice (both sexes, 8-10 wk age) were fed standard rodent (TD7012, reference) or high-fat, high-cholesterol-containing (TD88137, 21% fat, 0.15% cholesterol, 19.5% caesin) supplemented 5% GOS (TD170432, WD + GOS) for 16 wk. WD-fed gavaged daily curcumin (100 mg/kg) served positive controls. Glucose tolerance, colonic layer, gene expression, circulating macrophage/neutrophil levels determined. Hyperlipidemic Ldlr-/- without supplementation (for wk) used to assess plasma LPS Effects dietary on different parameters compared each genotype. RESULTS Compared WD, glucose tolerance was significantly improved male WD + GOS (mean ± SEM: AUC = 53.6 ± 43.9 45.4 ± 33.3 g ⋅ min/dL; P = 0.015). Continuity (MUC-2 expression) receiving supplementation, indicating barrier. also reduced macrophages (30% decrease) neutrophils (60% decrease), suggesting diminished systemic inflammation. In mice, concentrations 0.81 ±  0.43 EU/mL 0.32 ± 0.26 EU/mL, P   < 0.0001, females 0.56 ± 0.24 0.34 ± 0.12 P = 0.036, males), attenuated atherosclerotic lesion area 54.2% ± 6.19% 43.0% ± 35.12%,  = 0.0006, 54.6% ± 3.99% 43.1% ± 8.11%, P = 0.003, males). CONCLUSIONS improves attenuates diseases and, therefore, may represent novel strategy management these