Fenghao An

As one of the few carotenoid-producing microorganisms, Rhodotorula mucilaginosa remains underexplored for its antioxidant activity. This study investigated the effects of R. mucilaginosa JAASSRY on D-galactose-induced aging mice. The high-dose JAASSRY (HR) significantly increased body weight by 9.89% compared to the model group (AM), while reducing organ indices of the spleen, liver, kidneys, and brain (p < 0.01). Compared with the AM group, the HR group exhibited increased serum activities of SOD (20.26%), GSH-Px (9.03%), and CAT (133.01%), with a 24.87% decrease in MDA level. In brain tissue, SOD, GSH-Px, and CAT activities increased by 79.49%, 8.45%, and 60.23%, respectively, while MDA decreased by 8.29%. R. mucilaginosa JAASSRY also dose-dependently alleviated structural damage in the hippocampus and spleen and improved motor strength and learning-memory capacity. Furthermore, R. mucilaginosa JAASSRY increased the abundance of Lactobacillus and reduced Proteobacteria, Helicobacter, and Oscillospira, while enhancing antioxidant capacity by modulating nucleotide, lipid, and carbohydrate metabolism. Lactobacillus and Pediococcus were positively correlated with memory latency and CAT/SOD activities (p < 0.05), whereas Actinormyces and Dehalobacterium showed negative correlations. Notably, HR performed comparably or superiorly to β-carotene in improving cerebral oxidative stress and beneficial microbiota, suggesting its potential in neuroprotection and gut–brain axis regulation. In conclusion, R. mucilaginosa JAASSRY mitigates aging-related oxidative damage and behavioral deficits by modulating gut microbiota structure and function, demonstrating its promise as a β-carotene alternative in animal husbandry and functional foods.