Cell Biology, Research Institute, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Molecular Medicine Programs, Research Institute, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Nutrients. 2020 Nov 20;12(11):3557. doi: 10.3390/nu12113557.
The objective of this study was to characterize the early effects of high fructose diets (with and without high fat) on both the composition of the gut microbiota and lipid metabolism in Syrian hamsters, a reproducible preclinical model of diet-induced dyslipidemia. Eight-week-old male hamsters were fed diets consisting of high-fat/high-fructose, low-fat/high-fructose or a standard chow diet for 14 days. Stool was collected at baseline (day 0), day 7 and day 14. Fasting levels of plasma triglycerides and cholesterol were monitored on day 0, day 7 and day 14, and nonfasting levels were also assayed on day 15. Then, 16S rRNA sequencing of stool samples was used to determine gut microbial composition, and predictive metagenomics was performed to evaluate dietary-induced shifts in deduced microbial functions. Both high-fructose diets resulted in divergent gut microbiota composition. A high-fat/high-fructose diet induced the largest shift in overall gut microbial composition, with dramatic shifts in the Firmicute/Bacteroidetes ratio, and changes in beta diversity after just seven days of dietary intervention. Significant associations between genus level taxa and dietary intervention were identified, including an association with in high-fat/high-fructose fed animals and an association with with the low-fat/high-fructose diet. High-fat/high-fructose feeding induced dyslipidemia with increases in plasma triglycerides and cholesterol, and hepatomegaly. Dietary-induced changes in several genus level taxa significantly correlated with lipid levels over the two-week period. Differences in microbial metabolic pathways between high-fat/high-fructose and low-fat/high-fructose diet fed hamsters were identified, and several of these pathways also correlated with lipid profiles in hamsters. The high-fat/high-fructose diet caused shifts in the host gut microbiota. These dietary-induced alterations in gut microbial composition were linked to changes in the production of secondary metabolites, which contributed to the development of metabolic syndrome in the host.
本研究旨在描述高果糖饮食（高脂和低脂）对叙利亚仓鼠肠道微生物组成和脂质代谢的早期影响，叙利亚仓鼠是一种可重现的饮食诱导血脂异常的临床前模型。8 周龄雄性仓鼠喂食高脂/高果糖、低脂/高果糖或标准饲料 14 天。在基线（第 0 天）、第 7 天和第 14 天收集粪便。在第 0 天、第 7 天和第 14 天监测空腹血浆甘油三酯和胆固醇水平，第 15 天还测定非空腹水平。然后，通过 16S rRNA 测序对粪便样本进行肠道微生物组成分析，并进行预测宏基因组学分析，以评估饮食诱导的微生物功能变化。两种高果糖饮食导致肠道微生物组成的显著差异。高脂/高果糖饮食引起的整体肠道微生物组成变化最大，在仅仅 7 天的饮食干预后，厚壁菌门/拟杆菌门比值明显变化，β多样性也发生变化。在属水平分类群与饮食干预之间确定了显著的相关性，包括在高脂/高果糖喂养动物中与 的相关性和在低脂/高果糖饮食中与 的相关性。高脂/高果糖喂养诱导血脂异常，血浆甘油三酯和胆固醇升高，肝肿大。在两周的时间里，几种属水平分类群的饮食诱导变化与脂质水平显著相关。在高脂/高果糖和低脂/高果糖饮食喂养的仓鼠之间鉴定出微生物代谢途径的差异，其中一些途径也与仓鼠的脂质谱相关。高脂/高果糖饮食引起宿主肠道微生物群的变化。这些饮食诱导的肠道微生物组成改变与次生代谢产物的产生变化有关，这导致了宿主代谢综合征的发生。
