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

Abstract

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.

The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies

“…Studies have shown that changes in the gut microbiome can alter synaptic plasticity in the brain. For example, as recently reviewed, germ-free mice (raised without exposure to microorganisms) have impaired synaptic plasticity compared to conventionally-raised mice ( Glinert et al, 2022 ).…”

Causal associations between gut Bifidobacteriaceae and transplantation failure: A Mendelian Randomization Study

“…The microbiome-gut-brain axis is a bidirectional connection between intestinal bacteria and the brain, and synaptic plasticity is important in this axis (22). Interestingly, we discovered that genes harboring Bi dobacteriaceae abundance associated SNPs were primarily enriched in synapse related terms.…”

Cognitive impairment in psychiatric diseases: Biomarkers of diagnosis, treatment, and prevention

“…The gut microbiome is a complex microbial ecosystem that has been clearly shown to influence host psychological, emotional, and cognitive functions through various neurophysiological aspects of synaptic plasticity, and may be a key regulator of neural development of the microbiome-gut-brain axis ( Rogers et al, 2016 ; Glinert et al, 2022 ). Fecal transfer of gut microbiota from SCZ patients has been reported to induce SCZ-related behaviors in germ-free recipient mice, accompanied by alterations in levels of glutamate, glutamine and GABA in the hippocampus ( Zheng et al, 2019 ).…”