Aging-associated cognitive dysfunction has a great influence
on
the lifespan and healthspan of the elderly. Theaflavins (TFs), a mixture
of ingredients formed from enzymatic oxidation of catechins during
the manufacture of tea, have a positive contribution to the qualities
and antiaging activities of black tea. However, the role of TFs in
mitigating aging-induced cognitive dysfunction and the underlying
mechanism
remains largely unknown. Here, we find that TFs effectively improve
behavioral impairment via the microbiota–gut–brain axis:
TFs maintain gut homeostasis by improving antioxidant ability, strengthening
the immune response, increasing the expression of tight junction proteins,
restructuring the gut microbiota, and altering core microbiota metabolites,
i.e., short-chain fatty acids and essential amino acids (SCFAs and
AAs), and upregulating brain neurotrophic factors. Removing the gut
microbiota with antibiotics partly abolishes the neuroprotective effects
of TFs. Besides, correlation analysis indicates that the decrease
in gut microbiota, such as Bacteroidetes and Lachnospiraceae, and the increase in microbiota metabolites’
levels are positively correlated with behavioral improvements. Taken
together, our findings reveal a potential role of TFs in mitigating
aging-driven cognitive dysfunction via the microbiota–gut–brain
axis. The intake of TFs can be translated into a novel dietary intervention
approach against aging-induced cognitive decline.