Faecal transplant makes the brains of old mice act young again

A faecal microbiome transplant (FMT) could make an aged brain as adaptable as a young one. Our gut microbiome has been linked to our risk of depression and may even play a role in shaping our personality. But for the first time, a study has shown that older mice given the gut microbiomes of younger animals via an FMT experience improved brain plasticity. This suggests that they could overcome a condition similar to amblyopia, also known as lazy eye, which is typically only successfully treated in childhood.

“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,” says Parisa Gazerani at Oslo Metropolitan University in Norway, who wasn’t involved in the work. “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.”

Neuroplasticity, the brain’s ability to remodel itself, means that conditions like amblyopia can be treated in children by temporarily covering their stronger eye. This forces the brain to forge new connections to the weaker eye, improving overall vision. But plasticity peaks at a young age, decreasing as our brains naturally prune unused connections during adolescence.

Paola Tognini at the Sant’Anna School of Advanced Studies in Pisa, Italy, and her colleagues wanted to see whether the gut microbiome is involved in this and could be manipulated to boost brain plasticity in adulthood.

First, they gave 21-day-old mice a high dose of broad-spectrum antibiotics dissolved in water every day for 10 days, and found substantial changes to their gut microbiomes compared with a control group of mice that had untreated water. This included reduced levels of bacterial families such as Lachnospiraceae, which is involved in making short-chain fatty acids with neuroprotective properties.

Each mouse then had one eye sealed for three days. After this, when the researchers imaged the neural responses to the stimulation of each eye, they found that only the control mice showed evidence of neuroplasticity, with their brains responding more to stimulation of the eye that had stayed open.

To investigate what might be behind the change, the team did RNA sequencing to reveal which genes were switched on in the mice’s visual cortex. “We found dramatic alterations in the animals receiving the antibiotic cocktail,” says Tognini. More than 1000 genes were differently expressed in these mice compared with the control ones. These included genes related to the process of myelination, when nerves get wrapped in a protective sheath, and the permeability of the blood-brain barrier.

Finally, the team transplanted the faecal microbiota of mice aged around 30 days old into 4-month-old adult mice, while a control group received transplants from other adults. Only the brains of the mice receiving the young microbiota demonstrated neuroplasticity in response to the eye-shutting experiment.

If the same applies to people, the implications could be huge, says Harriët Schellekens at University College Cork in Ireland. “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 says. “The challenge will be to identify the specific microbial metabolites or strains responsible, rather than relying on crude microbiota transplants.”

However, direct extrapolation to people is premature, says Gazerani, primarily because our brains are more complex and our microbiomes are very influenced by our diet and lifestyles.

The study also raises questions about the potential long-term effects of early-life antibiotic exposure, says Gazerani, 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 says.