Overview
- Co-housing young with old mice transferred an aged microbiome and induced short-term memory deficits, which were reversed after microbiome depletion with antibiotics.
- A bacterium that expands with age, Parabacteroides goldsteinii, generated medium-chain fatty acids that activated peripheral macrophages through the receptor GPR84.
- This inflammatory cascade suppressed vagus-nerve input and reduced novelty-evoked hippocampal activity that supports memory formation.
- Targeted bacteriophages eliminating P. goldsteinii or pharmacologic GPR84 blockade (PBI-4050) restored hippocampal responses and rescued memory in aged or colonized mice.
- Vagal stimulation—including capsaicin, cholecystokinin, and GLP-1 agonists—also normalized cognition in mice, pointing to gut-focused strategies that have not yet been tested in humans.