Spermidine, an essential cellular polyamine that declines with age is increasingly recognized for its impact on longevity, cognitive performance, and cellular resilience. While oral spermidine shows benefits in animal models, much of its activity may originate in the gut, rather than through systemic elevation. To harness this gut-centric mechanism, researchers engineered the probiotic yeast Saccharomyces boulardii to overproduce and secrete spermidine directly in the gastrointestinal tract, ensuring targeted delivery with minimal impact on whole-body polyamine levels.
This spermidine-producing strain, Sb576, significantly protected against age-related short-term memory decline in Drosophila, outperforming both wild-type yeast and free spermidine. Remarkably, even short supplementation enhanced memory in both young and aged flies, including in a memory-deficient mutant strain (Dh31R), without affecting locomotion. These findings highlight the gut–brain axis as a key therapeutic node and demonstrate that in situ microbial production of spermidine may offer a potent strategy for preserving cognitive function during aging.
Source : https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1628160/full