The relationship between egg consumption and disturbances of hepatic lipid metabolism remains controversial.Recent studies indicate that egg consumption showed favorable effects on dyslipidemia, while underlying mechanisms remain largely undefined. In this study, the high-fat diet was fed to C57BL/6J mice to induce lipid metabolism disorders, aiming to disclose the effects of the whole eggs (WEs) and yolk-free egg substitute (YFES) on the hepatic lipid profile and gut microbiota. The daily WE/ YFES dose for mice was 7.55 mg/g of mouse weight. The results showed that WE inhibited body weight gain and significantly decreased hepatic triglyceride (TG) by 49.6% while showing insignificant effects on the total cholesterol in the liver. Both WE and YFES alleviated hepatic oxidative stress by decreasing hepatic levels of malondialdehyde. Lipidomic analysis revealed that diacylglycerol, lysophosphatidylcholines, ceramide, and free fatty acids were the major lipid species upregulated by WE. Moreover, WE showed beneficial effects on gut microbiota by increasing the abundance of Bacteroidota while decreasing Proteobacteria levels. The correlation analysis showed that Lactobacillales and Bacteroides displayed a significant negative correlation with hepatic TG and free fatty acids (18:4), while positively correlated with phosphatidylethanolamine biomarkers. These results evidenced that WE was more effective than YFES in improving hepatic lipid profiles and regulating the gut microbiota, resulting in increased levels of probiotics and inhibited TG accumulation and oxidative stress through the gut−liver axis. Therefore, it could be concluded that the consumption of WE instead of YFES would be helpful in relieving hepatic dyslipidemia in the short term.
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