2'‐Fucosyllactose attenuates aging‐related metabolic disorders through modulating gut microbiome‐T cell axis

Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including Ligilactobacillus, Colidextribacter, Mucispirillum, and Lachnoclostridium, and increased abundance of harmful bacteria including Turicibacter and Desulfovibrio, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.