Exploring the role of metabolic challenges and gut microbiota signals in brain function and plasticity

My PhD thesis investigates the profound influence of peripheral factors like diet and gut microbiota on brain function and neuroplasticity, challenging the conventional understanding that separates the brain from peripheral bodily processes. The thesis comprises two main studies that elucidate how metabolic states and environmental stimuli are integral to neural function, underscoring the interconnectivity between the brain and the body's overall physiological state.In the first study, we investigated the epigenetic and transcriptomic impact of fasting on the cerebral cortex. Utilizing ChIP-seq and RNA-seq techniques, we found that fasting led to an enhanced beta-hydroxybutyrylation of histone H3 in the brain, correlating with active gene expression. Particularly we observed changes in circadian rhythms and specific enduring alterations in circadian locomotion, illustrating fasting profound and lasting influence on brain function.The second study reveals that signals from the gut microbiota are crucial for enhancing the brain's plastic potential under environmental enrichment. Developmental analyses showed significant differences in the gut bacteria composition between mice reared in enriched (EE) versus standard (ST) environments, with corresponding changes in short-chain fatty acid (SCFA) levels. Depleting the microbiota with antibiotics or augmenting it via SCFA treatment underscored the essential role of the gut microbiota in modulating neuroplasticity. Transferring the microbiota from EE mice to ST mice activated neural plasticity, highlighting how peripheral microbial signals can directly influence brain plasticity.This research challenges the traditional perspective that brain function and plasticity are solely dependent on central nervous system activities proposing instead that peripheral factors significantly influence brain health and plasticity. This underscores the importance of a holistic approach in neuroscience, one that incorporates lifestyle factors into the study of brain processes and establishes a foundation for incorporating a broader physiological perspective into neuroscientific research. Moreover, the findings suggest that lifestyle changes could offer substantial, non-invasive improvements in cognitive function and overall brain health, leading to innovative therapeutic strategies that consider the entire organism.