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The microbiota-gut-brain axis and microbiome modulation in preclinical models of psychiatric disorders

We explore how genes and the environment combine via experience-dependent plasticity in the healthy
and diseased brain. Our research includes models of specific neurological and psychiatric disorders which involve cognitive and affective dysfunction, investigated at behavioural, cellular and molecular levels so as to identify pathogenic mechanisms and novel therapeutic targets. Most recently, this has included studies of intergenerational and transgenerational epigenetic inheritance.

Aims

Psychiatric disorders, including schizophrenia, depression and anxiety disorders, represent some of the greatest burdens of disease. Interestingly, chronic gastroenterological issues such as gut inflammation are common co-morbid symptoms of psychiatric disorders, including schizophrenia. The potential role for the microbiome in schizophrenia pathogenesis had been highlighted, and proposed to be dysregulated in schizophrenic patients compared to healthy controls. Thus, the collective evidence supports a role for the gut microbiome in schizophrenia pathogenesis, but the potential implications for new therapies remains to be investigated. This proposal will explore the status of the gut microbiota in a well-studied mouse model, followed by an exploration of how direct modulation of gut microbiota influences the behavioural and cognitive responses, as well as brain function and dysfunction.

Our findings will inform the role of gut microbiota dysbiosis in schizophrenia, uncovering new aspects of pathogenesis that could lead to novel therapeutic targets to improve the treatment of the cognitive, psychiatric and social symptoms. More broadly, there could also be implications for improving therapeutic approaches for other psychiatric disorders. This project will use microbial, environmental and pharmacological modulation, cognitive and behavioural tasks, as well as cellular and molecular approaches, including genetics, genomics and bioinformatics tools.

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