Impact of Lutein Supplementation on Liver Health, Oxidative Metabolism, Gut Microbiota, and Growth Performance in High-Fat Diet Fed Mice

Background/Objectives: Natural bioactive compounds are promising interventions for obesity-related metabolic dysfunction. Lutein, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, may improve metabolic health, but its effects on liver function and gut microbiota in high-fat diet (HFD)-induced obesity are not fully elucidated. This study evaluated the effects of lutein supplementation on hepatic function, oxidative status, lipid metabolism, and gut microbiota composition in HFD-fed mice. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to four groups (n = 8/group): Ctrl (low-fat diet), model (HFD), low-dose lutein (50 mg/kg/day), and high-dose lutein (100 mg/kg/day). Results: Following a 70-day intervention, lutein supplementation, particularly at the higher dose, reduced the liver index, improved serum lipid profiles, liver injury markers, and hepatic antioxidant capacity by increasing superoxide dismutase, catalase, and glutathione levels while reducing malondialdehyde content, and alleviated hepatic histopathological alterations. Lutein supplementation was also linked to elevated gut microbial richness and shifts in the relative frequency of several bacterial taxa, including partial restoration of Bacteroidota and enrichment of Roseburia and Faecalibaculum. These findings demonstrate that lutein supplementation attenuated HFD-induced metabolic and hepatic alterations, accompanied by improved antioxidant status and modulation of gut microbiota. Conclusions: Overall, lutein alleviated hepatic steatosis, oxidative stress, and metabolic dysfunction, highlighting its potential as a dietary strategy for managing obesity-related liver functions and gut dysbiosis.