A human milk oligosaccharide alters the microbiome, circulating hormones, cytokines and metabolites in a randomized controlled trial of older individuals

Aging-related remodelingdecline in immune function is associated with diseases like cancer, atherosclerosis, and neurodegenerative conditions. This study aimed to improve the aging gut microbiota and immune system by introducing 2-fucosyllactose (2'-FL), a common oligosaccharide found in human breast milk with established health benefits in infants and animal models. 2'-FL was consumed at either of two doses versus placebo by 89 healthy older individuals (average age = 67.3 years) in a 6-week randomized controlled trial. Although the primary endpoint (significant change in the cytokine response score) was not met, consumers of the prebiotic experienced increased levels of Bifidobacterium in the gut microbiota, along with elevated serum levels of insulin, high-density lipoprotein (HDL) cholesterol, and fibroblast growth factor 21 (FGF21) hormone. Additional metabolomic and proteomic changes were observed specifically in 2'-FL "responders" who experienced a bloom in Bifidobacterium. 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 to aging individuals.