Data from the Rejuvenating the Aging Microbiota with Prebiotics (RAMP) study found that six weeks of supplementation with five grams per day of 2′-fucosyllactose (2′-FL) improved levels of HDL cholesterol, insulin levels and FGF21, a hormone that plays a crucial role in regulating metabolism, energy expenditure and insulin sensitivity.
Writing in Cell Reports Medicine, the researchers noted that not all of the participants responded to the prebiotic treatment. Interestingly, the Bifidobacterium responders were also found to have improved performance on a cognitive test compared to non-responders, a result the study called “speculative”.
“These results demonstrate a potential impact of 2′-FL supplementation on cognitive function in human adults,” wrote the researchers, led by Stanford’s Dr. Justin Sonnenburg. “Previous work has shown that 2′-FL levels in breast milk are positively associated with cognitive development in human infants, and 2′-FL supplementation influences vagus-nerve-mediated memory adaptations in adult rodents.”
The benefits
HMOs are unique carbohydrates that make up about 10% of the dry weight of mother’s milk. HMOs are not easily digested, so experts postulate that their purpose is to jump-start the infant’s microbiome as prebiotics.
There are over 130 different HMOs, and 2’-FL (2’-fucosyllactose) is the most abundant. As a result, it is the most studied and is already commercially available from a number of different suppliers, including dsm-firmenich, Novonesis, IFF, BASF and Friesland Campina, to name a few.
The majority of the science to date has obviously focused on infants, with a 2016 study by scientists at Abbott Nutrition finding that infants fed a formula with 2’-FL had levels of inflammatory cytokines similar to those observed for breast feeding and significantly lower than those observed for infants fed a control formula containing no 2’-FL (Journal of Nutrition).
Another Abbott study, this one published in 2023 in Nutrients found that infant formula with 2′-FL could modulate an infant’s microbiome to support immune homeostasis. The data also showed that 2’-FL can elevate the production of secondary microbial metabolites in the infant’s microbiome to levels closer to that seen in breastfed infants.
At the other end of the age spectrum, the bifidogenic effects of HMOs may also benefit older populations, which are characterized by declining Bifidobacteria levels.
Combining 2’-FL with oligofructose may also produce important benefits in adults, according to findings published in the American Journal of Clinical Nutrition last year. Scientists from the University of Reading in the UK reported that the prebiotic combination could alter the microbial composition and alleviate stress-induced mood state in adults.
New data
The new study supports the benefits of HMOs in older adults and their potential for brain health.
Eighty-nine healthy older adults with a mean age of 67 years were recruited to participate in the randomized, placebo-controlled clinical trial. Participants were randomly assigned to receive placebo or low (1 gram per day) or high (5 grams per day) doses of 2’-FL for six weeks.
The data showed that 2’-FL supplementation did not impact cytokine response, which was the primary endpoint for the study. However, high dose 2′-FL supplementation was found to increase gut Bifidobacterium levels, with B. adolescentis and B. pseudocatenulatum displaying similar trends to the genus.
There was significant variability of the Bifidobacterium response, which led the researchers to classify participants as either “responders” or “non-responders”. Responders had more Bifidobacterium in their guts at the start of the study.
Intriguingly, Bifidobacterium “responders” were found to experience metabolic and inflammatory changes, in addition to performing better on visual memory tests.
“Our work demonstrates that dosing older adult humans with 2′-FL results in a targeted modification of the microbiota, namely a bloom of Bifidobacterium in the High Dose 2′-FL group,” the researchers wrote.
“… the bloom of Bifidobacterium was accompanied by widespread metabolic and immune alteration. Given that we show evidence of 2′-FL entering systemic circulation and that past work shows direct effects of 2′-FL on host cells, future work will be needed to determine the extent to which these HMO-mediated effects are dependent upon activity of the microbiota.”
Source: Cell Reports Medicine, 2025, Vol. 6, 102256. doi: 10.1016/j.xcrm.2025.102256. “A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults”. Authors: M.M. Carter, et al.
