Abstract
Aging-related immune dysfunction is linked to cancer, atherosclerosis, and neurodegenerative diseases. This 6-week randomized controlled trial evaluated whether 2'-fucosyllactose (2'-FL), a human breast milk oligosaccharide with established benefits in infants and animal models, could improve gut microbiota and immune function in 89 healthy older adults (mean age 67.3 years). While the primary endpoint of cytokine response change was not met, 2'-FL supplementation increased gut Bifidobacterium levels and elevated serum insulin, high-density lipoprotein (HDL) cholesterol, and FGF21 hormone. Bifidobacterium "responders" experienced additional metabolic and proteomic changes and also performed better on a cognitive test of visual memory. Nonresponders were more likely to lack Bifidobacterium in their gut microbiota at the start of the intervention. Multi-omics analysis indicated a systemic response to 2'-FL, which could be detected in blood and urine, showcasing the potential of this prebiotic to provide diverse benefits for healthy aging. This trial was registered at ClinicalTrials.gov (NCT03690999).