Abstract
Aim: 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. Methods: 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. Results: 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 Ruminococceace NK4A214 group in high-fat/high-fructose fed animals and an association with Butryimonas 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. Conclusions: 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.
Highlights
Human gut microbiota, comprising of bacteria, viruses, phages, fungi and protists, play a profound role in mammalian health, contributing to host metabolism [1], and to mucosal and systemic immune responses [2] and the metabolism of xenobiotics [3]
We evaluated total gross energy intake over the two-week no significant difference in energy intake between experiment diets intake when compared to control diet; experimental period and found no significant difference in energy between experiment diets animals fed with high-fat/high-fructose diet exhibited an increase in energy intake compared when compared to control diet; animals fed with high-fat/high-fructose diet exhibited an to low-fat/high-fructose hamsters increase in energy intake fed compared to(Figure low-fat/high-fructose fed hamsters (Figure 1B)
Feeding either high-fat/high-fructose or low-fat/high-fructose diets resulted in shifts in overall composition of the gut microbiota, with high-fat/high-fructose diet resulting in more profound changes in both the gut microbiota and lipid metabolic profiles compared to a low-fat/high-fructose diet
Summary
Human gut microbiota, comprising of bacteria, viruses, phages, fungi and protists, play a profound role in mammalian health, contributing to host metabolism [1], and to mucosal and systemic immune responses [2] and the metabolism of xenobiotics [3]. Over the last two decades, studies have focused on understanding the links between changes in the gut microbiota and the development of metabolic syndromes in humans, such as diabetes, obesity, and nonalcoholic fatty liver disease [1,6,7]. Both murine models and human studies reveal strong associations between alterations in the relative proportions of dominate gut phyla (that is, Bacteroidetes and Firmicutes) and obesity [8,9]. Recent work has determined one of the metabolic links between the gut microbiota and host cholesterol levels, with a microbial enzyme identified as a key factor in metabolizing dietary cholesterol, and subsequently limiting cholesterol absorption [11]
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