Theaflavins in Black Tea Mitigate Aging-Associated Cognitive Dysfunction via the Microbiota–Gut–Brain Axis

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.