Multi-omics investigation unveils the role of Eurotium cristatum fermentation in potentiating thinned young apple pomace for colitis-induced liver disorders amelioration.

Liver disorders are the most prevalent extraintestinal manifestations observed in patients with ulcerative colitis, impacting millions of individuals worldwide. The present study elucidated the novel role of Eurotium cristatum (E. cristatum) -fermented thinned young apples (E.YAP) in preventing colitis associated liver disorders and dissected potential mechanisms through multi-omics integration. Specifically, E.YAP exhibited superior efficacy in alleviating colitis symptoms, liver damage, lipid accumulation, inflammation cytokines and oxidative stress, compared to the unfermented sample and the anti-colitis drug mesalazine. Hepatic transcriptomics demonstrated that E.YAP suppressed genes belonging to the cytochrome P450 family, CXC chemokine ligands and pro-inflammatory cytokines while enhancing PPAR signaling and oxidative phosphorylation. E.YAP exclusively elevated hepatic levels of metabolites involved in glycerophospholipid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids and glutathione metabolism, whereas suppressing urobilin, a microbial metabolite implicated in fatty liver disease. Moreover, E.YAP increased α-diversity and relative abundances of Lactobacillus, Akkermansia, Muribaculum, Blautia and Faecalibaculum, concurrently increasing short-chain fatty acids. Multi-omics integration revealed robust links between E.YAP- affected hepatic genes, metabolites and gut bacteria that were associated with liver health. Furthermore, E.YAP outperformed unfermented samples in mitigating palmitic acid-induced inflammation, dyslipidemia and ROS overproduction in HepG2 cells. Additionally, network pharmacology identified key metabolites enriched by E. cristatum fermentation, particularly flavonoids, polyphenols and indole derivatives, which may synergistically inhibit hepatic inflammation and oxidative stress. Collectively, our study establishes the novel function of E.YAP in preventing colitis associated liver disorders, providing a sustainable strategy to valorize apple thinning waste into functional foods.