The composition of the gut microbiome has been shown to change with age, undergoing a loss of beneficial microbes in favor of inflammatory microbes that contribute to the chronic inflammation of aging and onset and progression of age-related conditions. Researchers have comprehensively demonstrated in animal models that introducing a young microbiome into an old animal via fecal microbiota transplantation produces a lasting rejuvenation of the gut microbiome and corresponding improvements in measures of health. Here, researchers show that these benefits include an improvement in memory function in old animals.
While transplanting the fecal microbiota from young to aged rodents has been extensively studied (that is, young FMT [yFMT]), its mechanism of alleviating working memory decline has not been fully elucidated. In this report, we aimed to investigate the effect of yFMT on the working memory of aged recipient rats performing delayed match-to-position (DMTP) tasks and the associated cellular and molecular mechanisms.
The results revealed that yFMT mitigated the decline in DMTP task performance of aged recipients. This improvement was associated with a reshaped gut microbiota and increased levels of brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 1, and synaptophysin, enhancing synaptic formation and transmission. The remodeling of the gut microbiome influenced peripheral circulation and the hippocampus and medial prefrontal cortex by regulating the Th17/Treg ratio and microglial polarization. Ultimately, interleukin-4 and interleukin-17 emerged as potential key molecules driving the beneficial effects of FMT.
These observations provide new insights into the gut-brain axis, emphasizing the connection between the gut and brain through the circulation system, and suggest an immunological mechanism that may help reverse age-related declines in the gut microbiota.
Link: https://doi.org/10.1016/j.neures.2025.04.005
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