Decoding the neurocircuitry of gut feelings: Region-specific microbiome-mediated brain alterations

Research in the last decade has unveiled a crucial role for the trillions of microorganisms that reside in the gut in influencing host neurodevelopment across the lifespan via the microbiota-gut-brain axis. Studies have linked alterations in the composition, complexity, and diversity of the gut microbiota to changes in behaviour including abnormal social interactions, cognitive deficits, and anxiety- and depressive-like phenotypes. Moreover, the microbiota has been linked with neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Interestingly, there appears to be specific brain regions governing the neurocircuitry driving higher cognitive function that are susceptible to influence from manipulations to the host microbiome. This review will aim to elucidate the region-specific effects mediated by the gut microbiota, with a focus on translational animal models and some existing human neuroimaging data. Compelling preclinical evidence suggests disruption to normal microbiota-gut-brain signalling can have detrimental effects on the prefrontal cortex, amygdala, hippocampus, hypothalamus, and striatum. Furthermore, human neuroimaging studies have unveiled a role for the microbiota in mediating functional connectivity and structure of specific brain regions that can be traced back to neurocognition and behavioural output. Understanding these microbiota-mediated changes will aid in identifying unique therapeutic targets for treating neurological disorders associated with these regions. •The gut microbiota mediate aspects of the brain in a region-specific manner•Manipulating microbiota can result in both immediate and persisting alterations across these regions.•These specific brain regions are interconnected via neuronal circuits that govern socio-cognitive function.•Translatable animal studies have elucidated the mechanisms underlying these region-specific changes.•Human neuroimaging studies have provided additional insight into the microbiota's ability to modulate brain function.