The selenium-enriched Rhodotorula mucilaginosa JAASRY1 improved oxidative stress during the aging process via the gut-liver-brain axis

Background Oxidative stress, induced by the aging process, has been demonstrated to engender a variety of deleterious effects on the organism. The effectiveness of selenium-enriched Rhodotorula mucilaginosa remains unproven. Methods In this study, selenium-enriched Rhodotorula mucilaginosa JAASRY1 ( Se-RMSRY ) was comprehensively characterized. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy was employed to analyze its morphology and the elemental distribution of selenium. Furthermore, the specific chemical forms of biogenic selenium in Se-RMSRY were identified and quantified using high-performance liquid chromatography-inductively coupled plasma mass spectrometry. The potential of Se-RMSRY to exert antioxidant mechanisms for anti-aging effects was then systematically elucidated. Animal behavioral tests demonstrated behavioral differences induced by Se-RMSRY , thereby evaluating the improvement in aging phenotypes. Histopathological analysis of the hippocampus, liver, and intestine was performed to examine structural integrity and pathological changes. Intracellular reactive oxygen species (ROS) levels were detected using fluorescence-based assays to confirm oxidative stress mitigation. Western blotting was employed to validate the expression of aging-related proteins. Additionally, gut microbiome analysis via 16S rRNA sequencing was carried out to explore the composition and diversity of gut microbiota, thereby uncovering potential links between antioxidant activity and gut health in the anti-aging process. Results The results showed that selenomethionine (SeMet) was the predominant bioselenium composition of Se-RMSRY , with a concentration of 1213.16 mg/kg. Furthermore, Se-RMSRY significantly enhanced intestinal homeostasis by enriching beneficial Lactobacillus sp. populations and reprogramming microbial metabolism toward carbohydrate utilization while suppressing amino acid metabolism in aging mice ( p < 0.05). Systemic antioxidant capacity was augmented via coordinated activation of the Nrf2/NQO1/HO-1 signaling pathway and glutathione metabolism, with concomitant reductions in hepatic and intestinal oxidative stress markers ( p < 0.05). The intervention attenuated apoptosis through Bcl-2/Bax pathway modulation and improved gut barrier integrity ( p < 0.05), while hippocampal CA1 neuronal preservation correlated with reduced anxiety-like behaviors and enhanced cognitive performance ( p < 0.05). Conclusion These findings establish Se-RMSRY as a promising dietary intervention against age-related pathologies through gut–microbiota–organ axis regulation, thereby addressing the previously unproven efficacy of Se-RMSRY in counteracting aging-related oxidative stress.