Faecal transplant restores plasticity in aged mouse brains

faecal microbiome – A new study in mice suggests that transferring gut microbiomes from young animals can reopen the brain’s “windows” of plasticity in older brains. Using broad-spectrum antibiotics to disrupt the microbiome, then testing an eye-sealing approach tied to neural fl

In a lab where the clock matters, researchers tried to force an older brain to behave like a younger one. They did it with something that usually lives far away from sight—gut bacteria—and with a test that depends on the brain’s ability to rewire itself.

The study’s starting point is the idea that the gut microbiome can shape how the brain works. Our gut bacteria have been linked to depression risk and may influence aspects of personality. but this work makes a more direct claim: older mice given gut microbiomes from younger animals via faecal microbiome transplant (FMT) showed improved brain plasticity.

The researchers compared that shift to a problem known for being treatable mainly in childhood: amblyopia. also called “lazy eye.” In children. clinicians can temporarily cover the stronger eye. forcing the brain to build new connections to the weaker one. That works because plasticity is highest early in life. Over time, as adolescence ends, the brain naturally prunes unused connections—closing the developmental windows when rewiring is easiest.

Parisa Gazerani at Oslo Metropolitan University in Norway. who was not involved in the work. framed the implication in terms of timing. “This study suggests that microbial communities may help regulate critical periods of brain development by defining when developmental windows of heightened plasticity open and close. ” she said. “It suggests that the gut microbiome may be an active developmental partner that helps shape neural circuit maturation alongside sensory experience. immune activity and genetic programming.”.

Paola Tognini at the Sant’Anna School of Advanced Studies in Pisa, Italy, and colleagues set out to test whether the gut microbiome is involved in that plasticity peak—and whether it can be manipulated later.

Their first step disrupted the microbiome in very young mice. The team gave 21‑day‑old mice a high dose of broad-spectrum antibiotics dissolved in water every day for 10 days. They compared the results to a control group of mice given untreated water. The antibiotic-treated animals showed substantial changes to their gut microbiomes. including reduced levels of bacterial families such as Lachnospiraceae. a group involved in producing short-chain fatty acids with neuroprotective properties.

Then came the eye-sealing experiment. Each mouse had one eye sealed for three days. When the researchers imaged neural responses to stimulation of each eye, only the control mice showed evidence of neuroplasticity—brains responded more to the eye that had stayed open.

To understand what the antibiotic cocktail might be changing. the team performed RNA sequencing to see which genes were switched on in the visual cortex. “We found dramatic alterations in the animals receiving the antibiotic cocktail,” Tognini said. More than 1,000 genes were differently expressed in those mice compared with controls. The changes included genes related to myelination. the process in which nerves are wrapped in a protective sheath. and genes tied to blood-brain barrier permeability.

The most striking part of the work came next, when the researchers attempted a direct microbial “swap” in older animals. They transplanted faecal microbiota from mice aged around 30 days old into 4‑month‑old adult mice. A control group received transplants from other adults.

After the transplants, the team repeated the eye-shutting test. Only the brains of the mice receiving the young microbiota demonstrated neuroplasticity in response to the eye-sealing experiment.

Harriët Schellekens at University College Cork in Ireland said the results, if they translate to people, could be significant. “It would suggest that the microbiome is not only important for early-life brain development. but might also be targeted later in life to enhance learning. recovery after injury. or resilience in ageing and neurological disease. ” she said. But she also pointed to the hard part of turning experiments like this into therapies. “The challenge will be to identify the specific microbial metabolites or strains responsible, rather than relying on crude microbiota transplants.”.

Gazerani agreed that the findings raise a powerful possibility, but cautioned against assuming the same story will unfold in humans. Direct extrapolation is premature, she said, primarily because human brains are more complex and our microbiomes are shaped strongly by diet and lifestyle.

The research also puts a spotlight on another practical concern: what antibiotics—especially early in life—might be doing to the developing brain. Gazerani said the study raises questions about potential long-term effects of early-life antibiotic exposure. particularly if the dose is high and prolonged. “Although antibiotics remain lifesaving and should never be withheld when clinically indicated. these findings reinforce the importance of using them judiciously during critical developmental windows. ” she said.

In the mouse experiments. the gut microbiome looked less like background noise and more like a timing mechanism—something that can open and close the conditions under which the brain is ready to change. The next challenge is deciding what. exactly. in that microbial ecosystem controls the timing—and whether the same levers exist in people. without unintended consequences.

faecal microbiome transplant gut microbiome neuroplasticity amblyopia lazy eye antibiotics blood-brain barrier myelination short-chain fatty acids RNA sequencing mice