The combination of metagenome and metabolome to compare the differential effects and mechanisms of fructose and sucrose on the metabolic disorders and gut microbiota in vitro and in vivo

Sucrose and fructose are the most commonly used sweeteners in the modern food industry, but there are few comparative studies on the mechanisms by which fructose and sucrose affect host health. The aim of the present study was to explain the different effects of fructose and sucrose on host metabolism from the perspective of gut microbiota. Mice were fed for 16 weeks with normal drinking water (CON), 30% fructose drinking water (CF) and 30% sucrose drinking water (SUC). Compared with fructose treatment, sucrose caused significantly higher weight gain, epididymal fat deposition, hepatic steatosis, and jejunum histological injury. Sucrose increased the abundance of LPS-producing bacteria which was positively correlated with obesity traits, while fructose increased the abundance of Lactobacillus. An in vitro fermentation experiment also showed that fructose increased the abundance of Lactobacillus, while sucrose increased the abundance of Klebsiella and Escherichia. In addition, combined with microbial functional analysis and metabolomics data, fructose led to the enhancement of carbohydrate metabolism and TCA cycle capacity, and increased the production of glutamate. The cross-cooperation network greatly influenced the microbiota (Klebsiella, Lactobacillus), metabolites (glutamate, fructose 1,6-biosphosphate, citric acid), and genes encoding enzymes (pyruvate kinase, 6-phosphofructokinase 1, fructokinase, lactate dehydrogenase, aconitate hydratase, isocitrate dehydrogenase 3), suggesting that they may be the key differential factors in the process of fructose and sucrose catabolism. Therefore, the changes in gut microbiome mediated by fructose and sucrose are important reasons for their differential effects on host health and metabolism.