red pigments alleviate high-fat and high-sugar diet-induced NAFLD in mice by modulating the gut microbiota and metabolites.

red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet-induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS-induced alterations in body weight, lipid profiles, and liver function ( < .01). MRP supplementation decreased the abundance of , , , and , while increasing , , and in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of , , , , and ( < .01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food.