A team of Italian researchers has shown that gut bacteria from juvenile mice can reopen a critical window of brain plasticity in adults, raising fundamental questions about how the microbiome shapes neural development.
The study, posted as a preprint on bioRxiv, found that adult mice (4 months old) that received fecal microbiota transplants from juvenile donors (1 month old) regained the ability to rewire their visual cortex after monocular deprivation, a form of plasticity normally lost after the juvenile critical period closes.
Important clarification: Despite headlines claiming the transplants made “old mice act young again,” the recipients were young adult mice, not aged or senescent animals. The study addresses the reopening of developmental critical periods in adults, a very different question from reversing age-related cognitive decline.
The team, led by Paola Tognini at the Sant’Anna School of Advanced Studies in Pisa, first established that the gut microbiome is necessary for critical-period plasticity to occur. They treated mice from weaning (day 21) with a broad-spectrum antibiotic cocktail in drinking water, then tested their visual cortex plasticity at day 28-31 by sealing one eye for three days and measuring how the brain shifted its response toward the open eye.
Control mice showed a significant plasticity shift (p = 0.006). Antibiotic-treated mice showed none (p = 0.274).
The antibiotic-treated mice also had:
- 1,083 differentially expressed genes in the visual cortex (443 up, 640 down)
- Increased density of parvalbumin-positive (PV+) interneurons (p < 0.0001 per slice)
- Greater blood-brain barrier permeability (p = 0.036)
- Decreased LINGO1 (a negative regulator of myelination) (p = 0.018)
Having established that antibiotics abolished plasticity, the team then tested whether microbiota could restore it. Adult mice (4 months old) received fecal transplants from either juvenile donors (~day 28-30), adult donors (age-matched), or a PBS sham.
Only mice receiving juvenile microbiota showed restored ocular dominance plasticity. Adult-to-adult transplants and sham treatment had no effect.
The team identified 11 bacterial taxa enriched in the juvenile microbiome, many of them short-chain fatty acid (SCFA) producers, that may act as “pro-plasticity” signals influencing interneuron maturation, myelination, and blood-brain barrier integrity.
What it means
“This suggests the microbiome doesn’t just influence adult brain function, it plays an active role in defining when developmental windows of heightened plasticity open and close,” says Francesca Damiani, the study’s first author.
The finding adds to a growing body of evidence linking gut bacteria to brain development, including connections to autism, anxiety, and learning. But the mechanism is still unclear: the specific metabolites that drive the effect have not been identified.
The caveats
The study is a preprint and has not yet undergone peer review.
The exaggerated “old mice” framing in earlier coverage misrepresents what was actually tested. The adult recipients were 4 months old, equivalent to a young adult human, not an elderly one. Whether similar plasticity reopening works in aged mice remains unknown.
The plasticity model used, ocular dominance shift in the visual cortex, is a highly specific assay. Whether the findings generalize to other brain regions (hippocampus, prefrontal cortex) or to cognitive functions like learning and memory has not been tested.
The antibiotic cocktail used was high-dose and broad-spectrum, far beyond typical clinical exposure. And as noted by Harriët Schellekens, a microbiome researcher at University College Cork, the challenge is identifying specific microbial strains and metabolites rather than using whole-crude transplants.
What’s next
The Tognini lab is now working to isolate the specific microbial metabolites that drive the plasticity effect, with the goal of identifying synthetic compounds that could achieve the same result without live bacteria transplantation.
Source
Damiani F, Changizi Ashtiani K, Tognozzi A, et al. “The Critical Period Microbiota Shape Brain Plasticity.” bioRxiv (2026). DOI: 10.64898/2026.06.08.730811
Disclosure: Based on a preprint that has not undergone peer review.
Funding: Italian Ministry of University and Research (NextGenerationEU, PRIN 2022-BAGEL); NIH R01GM123558.