Ellagic acid (EA) exhibits potential antiaging activity.
Differences
in individual ability to produce urolithins may result in large interindividual
variability in the health effects of EA. Therefore, the effects and
mechanism of EA on d-galactose-induced aging, considering
urolithin A-producing ability, were investigated. Our results showed
that EA improved cognitive impairment and hippocampal damage, increased
the GABA (by 107.84–117.86%) and 5-HT (by 72.56–100.85%)
levels, and suppressed the inflammatory and oxidative stress in aging
rats. Thirteen plasma metabolites and 12 brain metabolites were improved
by EA administration in aging rats. In particular, EA showed a better
anti-aging effect in high-UroA-producing rats than in the low counterparts,
while antibiotic intervention almost offset EA-alleviated aging induced
by d-gal. Furthermore, the lower ratio of Firmicutes and
Bacteroidota as well as the greater abundances of Akkermansia (by 139.21%), Bifidobacterium (by 88.04%), Clostridium_sensu_stricto_1 (by 183.47%), Lactobacillus (by 97.23%), and Turicibacter (by 83.06%) were
observed in the high-UroA-producing group compared with the model
group (p < 0.05). These findings provide novel
insights into the anti-aging effects of EA and suggest that the ability
of the gut microbiota responding to EA largely determines EA’s
anti-aging performance.