Synergistic Effects of Fructose and Food Preservatives on Non-Alcoholic Fatty Liver Disease: From Gut Microbiome Alterations to Hepatic Gene Expression

Background Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of NAFLD in a human-microbiota-associated mouse model. Results Our comprehensive analysis reveals that fructose and potassium sorbate synergistically increase liver damage, inflammation, and fibrosis, while altering liver function, lipid profiles, and intestinal permeability. Significant changes were observed in the composition of gut bacterial and fungal communities, accompanied by the induction of predominantly pro-inflammatory immune responses, particularly in the mesenteric lymph nodes. Gene expression analysis in the liver uncovered extensive transcriptional changes induced by fructose and modulated by preservatives, affecting key genes involved in lipid metabolism, oxidative stress, and inflammatory responses. Conclusions Our findings highlight the complex interplay between dietary components, gut microbiota, and host metabolism in the development of NAFLD. The study suggests potential risks associated with combined fructose and preservative consumption, particularly potassium sorbate. These results open new avenues for understanding and treating NAFLD through dietary intervention and microbiome modulation, emphasizing the need for further investigation into the impact of food additives on liver health.