PALO ALTO, Calif.: Age-related memory decline was causally linked to gut bacteria in mice, Arc Institute and Stanford University researchers reported March 11 in the peer-reviewed journal Nature.
The team co-housed two-month-old mice with 18-month-old animals and transferred aged microbiomes into young germ-free mice. Recipients developed poorer short-term object recognition and spatial learning, while old germ-free mice showed slower cognitive decline, according to the published study.
Researchers identified Parabacteroides goldsteinii as a leading microbial driver. The bacterium produced medium-chain fatty acids that activated inflammatory myeloid cells through the GPR84 receptor, weakening sensory signals carried by the vagus nerve to the hippocampus, the paper said.
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Memory performance improved when researchers targeted different parts of that pathway. A bacteriophage directed against Parabacteroides, GPR84 inhibition and restoration of vagal activity each enhanced memory in aged mice. The GLP-1 receptor agonist liraglutide also improved their performance.
The findings do not show that gut-targeted treatments reverse age-related memory decline in humans. “Our study was exclusively done in mice,” first author Timothy O. Cox, an MD-PhD student at the University of Pennsylvania, wrote in an Arc Institute research summary.
Senior authors Maayan Levy and Christoph A. Thaiss are assistant professors of pathology at Stanford University and investigators at the Arc Institute.
The researchers said they were examining whether the pathway operates in humans and contributes to neurodegeneration or dementia.
