Unravelling the role of microbiota-gut-brain signalling in driving social, reward and motivational processes
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Date
2026-01-15
Authors
Sharvin, Brendan L.
Journal Title
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Publisher
University College Cork
Published Version
Abstract
The gut microbiota has been shown to influence mammalian physiology throughout development from critical windows of early life to later stages of adulthood. The last two decades of research has uncovered a role for these microorganisms in shaping host brain function and behaviour via the microbiota-gut-brain axis. Recent evidence suggests complex interactions between the microbiota and host can signal to distinct brain regions and networks driving higher-order behavioural paradigms.
In this thesis, I aim to further untangle the role of the gut microbiota in shaping higher-order behaviours, with a specific focus on social behaviour, motivational responses and reward processing. To this end, I utilised animal models of disrupted
gut microbiota composition. Specifically, we used a c-section (CS) combined with postnatal antibiotic (ABX) administration (CS-ABX) mouse model and discovered that an early life perturbation to the gut microbiota resulted in enduring neurobehavioral consequences later in life, specifically related to social and anxiety-like behaviour. Moreover, we showed that chronic administration with a bacterial probiotic strain was able to reverse these deficits in social behaviour. Using a combination of transcriptomic and metabolomic tools, we were able to further untangle the neurochemical consequences driving these behavioural changes in the amygdala and prefrontal cortex (PFC): two brain regions critical for emotional regulation and social interaction.
Later, we explored another model of disrupted gut microbiota composition using a broad-spectrum ABX cocktail. Interestingly, we demonstrated that ABX-treated mice elicited a significant increase in motivation to obtain a palatable reward in an operant conditioning paradigm. Interestingly, this corresponded with distinct changes in gene pathways within the nucleus accumbens (NAc), a neural hub for the integration of reward processing and motivation, along with a significant reduction in gut microbialassociated metabolites in the caecum. Furthermore, we showed that the dynamic state of the gut microbiota partially impacts motivational responses. We also observed that some of the ABX-induced effects on the host were prevented with an ablation of vagal signals via subdiaphragmatic vagotomy (SDV), however the effect
on motivational responses persisted.
Finally, we wanted to establish the technique of fiber photometry in our lab as a tool to comprehend gut microbial-mediated effects on in vivo neural dynamics. To this end, we designed a custom-built recording frame and ran a pilot study to understand the inter-individual dopamine responses to palatable rewards and investigate a role for the gut microbiota. Through establishing this technique in our lab for the first time, we have designed a framework for future investigations into untangling gut microbiota-mediated effects on in vivo neural dynamics.
Taken, together this work has made a substantial contribution into understanding the role of the gut microbiota in mediating social, reward and motivational processes and the distinct effects on brain regions critical for driving these behaviours.
Moreover, we have established tools in the lab that can be used for future mechanistic investigations using powerful brain recording technology.
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Controlled Access
Keywords
Microbiota , Social behaviour , Reward processing , Motivational behaviour , Amygdala , Prefrontal cortex , Nucleus accumbens
Citation
Sharvin, B. L. 2026. Unravelling the role of microbiota-gut-brain signalling in driving social, reward and motivational processes. PhD Thesis, University College Cork.