Faecal transplant makes the brains of old mice act young again

Introducing younger gut microbiomes into older mice can potentially make their brains more adaptable, akin to those of younger mice. This connection between our gut microbiome and psychological aspects like depression and personality is well-established. However, a new study reveals that older mice receiving gut microbiomes from younger mice through a faecal microbiome transplant (FMT) exhibit enhanced brain plasticity. This enhancement may help address conditions like amblyopia, or lazy eye, usually treatable only in childhood.

“This study suggests that microbial communities may regulate critical periods of brain development by determining when windows of heightened plasticity open and close,” states Parisa Gazerani from Oslo Metropolitan University in Norway, who was not part of the study. According to her, the gut microbiome might play an active role in neural circuit maturation alongside sensory experiences, immune responses, and genetic factors.

Neuroplasticity, the brain’s ability to reorganize itself, is crucial for treating conditions like amblyopia in children. By covering the stronger eye temporarily, the brain is encouraged to develop connections with the weaker eye, thus enhancing vision. This plasticity is most pronounced in young brains and diminishes as people age and unused connections are pruned during adolescence.

Paola Tognini from the Sant’Anna School of Advanced Studies in Pisa, Italy, and her team explored the role of the gut microbiome in brain plasticity and its potential manipulation to boost this adaptability in adults.

Initially, they administered a high dose of broad-spectrum antibiotics in water to 21-day-old mice for ten days. This led to significant changes in their gut microbiomes compared to a control group given untreated water. Notably, there was a reduction in bacterial families like Lachnospiraceae, known for producing neuroprotective short-chain fatty acids.

Each mouse then had one eye sealed for three days. Subsequent imaging of neural responses revealed that only the control group showed signs of neuroplasticity, with their brains responding more to stimulation of the open eye.

To uncover the mechanisms behind these observations, the team conducted RNA sequencing on the visual cortex of the mice. “We found dramatic alterations in the animals receiving the antibiotic cocktail,” Tognini reports. Over 1000 genes were expressed differently in these mice compared to controls, including those related to myelination and blood-brain barrier permeability.

Lastly, the researchers transplanted faecal microbiota from 30-day-old mice into 4-month-old adult mice, while another group received transplants from other adults. Only the mice with young microbiota demonstrated neuroplasticity during the eye-shutting experiment.

If similar effects occur in humans, the potential benefits could be substantial, suggests Harriët Schellekens at University College Cork in Ireland. She notes that targeting the microbiome might enhance learning, recovery after injury, or resilience in aging and neurological diseases. However, identifying specific microbial metabolites or strains is necessary rather than relying on broad microbiota transplants.

Nonetheless, Gazerani advises caution in applying these findings to humans, as our brains are more complex and influenced by diet and lifestyle. The study also prompts considerations regarding the long-term effects of early antibiotic exposure, especially with high or prolonged doses. “While antibiotics are lifesaving and should be used when needed, these findings highlight the importance of careful use during critical developmental stages,” she states.