Overview
- Young mice given an aged microbiome by co-housing or fecal transfer developed short- and long-term memory deficits, which were prevented or reversed by antibiotics or germ-free conditions.
- Parabacteroides goldsteinii expanded with age and produced medium‑chain fatty acids that activated GPR84 on gut myeloid cells, elevating TNF and IL‑1β and damping TRPV1/PHOX2B vagal afferents and hippocampal novelty responses.
- Multiple interventions restored cognition in mice, including a bacteriophage targeting P. goldsteinii, chemogenetic or pharmacologic activation of vagal/TRPV1 pathways, capsaicin, and treatment with CCK or GLP‑1 receptor agonists.
- Mice lacking GPR84 or depleted of myeloid cells were protected from MCFA‑ or microbiome‑induced impairments, substantiating a required immune step in the gut–brain pathway.
- Complementary PLOS Biology research found that high‑fat diet dysbiosis enabled live gut bacteria to reach the brain via the vagus nerve in mice, highlighting gut–vagus routes that still require human validation.