We investigated the effect of a high fructose diet (HFD) on Sprague Dawley rats and the impact of a synbiotic composed of Lactobacillus fermentum CECT5716 and fructooligosaccharides. Feeding the HFD for 5 weeks resulted in liver steatosis and insulin resistance but not obesity. These changes were associated with increased production of short-chain fatty acids and increased Bacteroidetes in feces, with an augmented Bacteroidetes/Firmicutes ratio, among other changes in the microbiota. In addition, barrier function was weakened, with increased LPS plasma levels. These data are consistent with increased fructose availability in the distal gut due to saturation of absorptive mechanisms, leading to dysbiosis, endotoxemia, hepatic steatosis, and insulin resistance. Treatment with the synbiotic prevented some of the pathological effects, so that treated rats did not develop steatosis or systemic inflammation, while dysbiosis and barrier function were greatly ameliorated. In addition, the synbiotic had hypolipidemic effects. The synbiotic composed by L. fermentum CECT5716 and fructooligosaccharides has beneficial effects in a model of metabolic syndrome induced by a HFD, suggesting it might be clinically useful in this type of condition, particularly considering that high fructose intake has been related to metabolic syndrome in humans.