Abstract：Camellia oleifera oil deodorizer distillate (CODD) is rich in high-value lipid components such as phytosterols, vitamin E, and unsaturated fatty acids, yet its direct utilization as a feed additive is hampered by poor dispersibility and low bioavailability. To develop green feed additives as alternatives to dietary antibiotics and achieve high-value utilization of CODD. In this study, Paecilomyces cicadae was inoculated into a solid-state fermentation system with soybean meal and wheat bran as carriers to ferment CODD. Non-targeted metabolomics combined with multivariate statistical analysis, KEGG pathway enrichment, and FELLA(functional enrichment analysis and visualization using sparse network-based activity diffusion) network analysis was employed to systematically elucidate the differential characteristics and regulatory mechanisms of lipid metabolism before and after fermentation. The results showed that the metabolic profiles of the fermentation and control groups exhibited significant separation. The expression patterns of differential lipid metabolites could be categorized into 4 functional groups: Comprehensive up-regulation of flavonoids (e.g., chrysin increased by over 4-fold), bidirectional regulation of steroids (anti-inflammatory pregnanes up-regulated while inert sterones down-regulated), uniform down-regulation of pro-inflammatory prostaglandins, and significant up-regulation of terpenoids. Mechanistic studies revealed that cutin/suberine/wax biosynthesis, steroid hormone biosynthesis, and arachidonic acid metabolism constitute 3 core regulatory pathways. The FELLA (functional enrichment analysis and visualization using sparse network-based activity diffusion) network further elucidated a cross-pathway synergistic regulatory mechanism with diacylglycerol and phosphatidylethanolamine as hub nodes and lipolytic enzymes together with acyltransferases as key enzyme targets. In conclusion, P. cicadae fermentation achieves pre-conversion of inert plant sterols present in CODD into highly active C21 steroids and directional restructuring of hesperetin-type precursor flavonoids into anti-inflammatory flavonoids such as chrysin, thereby enhancing the anti-inflammatory and antioxidant functional potential of the fermented products. This study provides a theoretical basis for the resource utilization of CODD and the development of green feed additives.
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