High Fructose Causes More Prominent Liver Steatohepatitis With Leaky Gut Similar to High Glucose Administration in Mice and Attenuation by Lactiplantibacillus plantarum dfa1

High-sugar diet-induced prediabetes and obesity is a current worldwide important problem that can be the result of glucose or fructose. However, a head-to-head comparison between both sugars on health impact is still less and Lactiplantibacillus plantarum dfa1 has never been tested and recently isolated from healthy volunteers. The mice with high-sugar diet-induced prediabetes and in vitro experiments were then performed. After 12 weeks of experiments, both glucose and fructose induced a similar severity of obesity (weight gain, lipid profiles and fat deposition at several sites) and prediabetes condition (fasting glucose, insulin, oral glucose tolerance test, and Homeostatic Model Assessment for Insulin Resistance (HOMA score)). However, fructose administration induced more severe liver damage (serum alanine transaminase, liver weight, histology score, fat components, and oxidative stress) than the glucose group, while glucose caused more prominent intestinal permeability damage (FITC-dextran assay) and serum cytokines (TNF-α, IL-6, and IL-10) compared to the fructose group. Interestingly, all these parameters were attenuated by L. plantarum dfa1 administration. Because there was a subtle change in the fecal microbiome analysis of mice with glucose or fructose administration compared to control mice, probiotics altered only some microbiome parameters (Chao1 and Lactobacilli abundance). For in vitro experiments, glucose induced more damage to high-dose lipopolysaccharide (LPS) (1 µg/mL) to enterocytes (Caco2 cell) than fructose, as indicated by transepithelial electrical resistance (TEER), supernatant cytokines (TNF-α and IL-8), and glycolysis capacity (by extracellular flux analysis). Meanwhile, both glucose and fructose similarly facilitated LPS injury in hepatocytes (HepG2 cell) as evaluated by supernatant cytokines (TNF-α, IL-6, and IL-10) and extracellular flux analysis. In conclusion, glucose possibly induced a more severe intestinal injury (perhaps due to LPS-glucose synergy) and fructose caused a more prominent liver injury (possibly due to liver fructose metabolism), despite a similar effect on obesity and prediabetes. Prevention of obesity and prediabetes with probiotics was encouraged.