Microbes, metabolites and (synaptic) malleability, oh my! The effect of the microbiome on synaptic plasticity.

The microbiome influences the emotional and cognitive phenotype of its host, as well as the neurodevelopment and pathophysiology of various brain processes and disorders, via the well-established microbiome-gut-brain axis. Rapidly accumulating data link the microbiome to severe neuropsychiatric disorders in humans, including schizophrenia, Alzheimer's and Parkinson's. Moreover, preclinical work has shown that perturbation of the microbiome is closely associated with social, cognitive and behavioural deficits. The potential of the microbiome as a diagnostic and therapeutic tool is currently undercut by a lack of clear mechanistic understanding of the microbiome-gut-brain axis. This review establishes the hypothesis that the mechanism by which this influence is carried out is synaptic plasticity - long-term changes to the physical and functional neuronal structures that enable the brain to undertake learning, memory formation, emotional regulation and more. By examining the different constituents of the microbiome-gut-brain axis through the lens of synaptic plasticity, this review explores the diverse aspects by which the microbiome shapes the behaviour and mental wellbeing of the host. Key elements of this complex bi-directional relationship include neurotransmitters, neuronal electrophysiology, immune mediators that engage with both the central and enteric nervous systems and signalling cascades that trigger long-term potentiation of synapses. The importance of establishing mechanistic correlations along the microbiome-gut-brain axis cannot be overstated as they hold the potential for furthering current understanding regarding the vast fields of neuroscience and neuropsychiatry. This review strives to elucidate the promising theory of microbiome-driven synaptic plasticity in the hope of enlightening current researchers and inspiring future ones.