Data published in Frontiers in Neuroscience indicated that the benefits were not observed when fruit flies (Drosophila melanogaster) were supplemented with free spermidine or non-engineered Sacchromyces boulardii.
“We have demonstrated that supplementation of D. melanogaster food with the engineered spermidine-secreting Sb [S. boulardii] strain Sb576 reduced aging-related decline in learning and [short-term] memory (STM),” wrote scientists from Ottawa Hospital Research Institute, the University of Ottawa, The Hospital for Sick Children Research Institute (Toronto), Carleton University and the University of Toronto.
“Moreover, we have shown that short-term (3 days) Sb576 supplementation enhanced STM in young flies, as well as in aged flies with memory deficit. This memory enhancement was unique to Sb576 and not shared by supplementation with either the SbWT control strain or free spermidine (1 mM).
“Furthermore, enhancement of learning and memory by Sb576 is not accompanied by enhancement of locomotive ability, suggesting that dietary Sb576 supplementation specifically influences brain functions.”
Building the science
Originally isolated from human semen in the 1920s, following the 1678 discovery of related polyamine compound spermine by Dutch microscopist Antonie van Leeuwenhoek, it was not until the mid-19th century that scientists discovered that spermidine was not unique to semen but ubiquitous in all living cells.
Spermidine began to draw increasing attention in the 1990s for its role in cellular homeostasis and autophagy—the body’s way of cleaning out damaged cells. Along with spermine and fellow polyamine putrescine, it has been shown to provide potent antioxidant and anti-inflammatory properties, cell and gene protection and autophagy activation.
In 2009, a key study published in Nature Cell Biology sparked further interest in the compound’s associations with anti-aging, neuroprotection and cardiovascular health, and a series of epidemiological studies followed, linking higher spermidine intake with longer lifespan and reduced incidence of age-related diseases.
“The diverse health benefits of spermidine supplementation, often at doses that do not significantly alter spermidine levels of target organs, suggests that exogenous spermidine may have a common site of action, the gastrointestinal (GI) tract,” explained the Ottawa- and Toronto-based scientists.
Study details
The study with fruit flies follows a paper published in Scientific Reports earlier this year that supported the viability of the spermidine-secreting strain in the guts of lab mice and increased levels of spermidine in the feces. In addition, the strain significantly reduced IBD symptoms and colitis-associated colon cancer in mice.
For the new study, the researchers investigated the effects of the spermidine-producing yeast on age-related declines in learning and memory using olfactory classical conditioning assay in fruit flies. The flies were divided into three groups: One group had diets supplements with live Sb576, one group received live non-engineered (wild-type) S. boulardii, and the third group fed on diets supplements with free spermidine.
After 30 days of feeding, the data indicated that aging-associated short-term memory (STM) decline was only reduced in the Sb576-fed flies and not in the other two groups.
“Notably, Sb576 supplementation, but not SbWT or spermidine supplementation, of either young flies or old flies for only three days also enhanced STM without affecting locomotive ability,” the researchers wrote.
They also tested the effects of Sb576 supplementation in a mutant strain of flies that is bred to exhibit compromised learning and memory. Results of this experiment showed that Sb576 again reduced the age-related declines in memory.
“These results demonstrate that in situ production of spermidine by a synthetic biotic yeast in the GI tract can enhance STM and further suggest a mechanism involving the gut-brain axis,” they wrote.
Next steps
Johné Liu, PhD, senior scientist and professor at Ottawa Hospital Research Institute and corresponding author on the new paper, told NutraIngredients: “Regarding the impact of Sb576 on neurofunctions, our next step is to extend the study in a mammalian species such as mice.”
He confirmed that the research team is seeking partnerships to further develop Sb576.
Source: Frontiers in Neuroscience, 2025, Volume 19. doi: 10.3389/fnins.2025.1628160. “Engineered spermidine-secreting Saccharomyces boulardii enhances olfactory memory in Drosophila melanogaster”. Authors: F. Parweez, et al.
