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Interventions targeting the brain-gut microbiome system.

To further investigate changes within the brain and gut system related to altered eating patterns and obesity and to determine causality, longitudinal studies with targeted interventions are needed. Clinical data suggests that the therapeutic effect of cognitive behavioral therapy (CBT) strengthens prefrontal inhibitory influences via cortico-limbic control circuits on regions of the reward, emotion regulation, and central autonomic networks. Animal models suggest that both diet and gut commensal bacteria influence ingestive behavior and central appetite regulation.

Intervention studies targeting the brain gut system will identify specific changes at different levels of the brain gut system related to each intervention, elucidating causality between gut microbes and inflammatory markers and behavior.

In order to identify candidate symptom-inducing microbe-metabolite-immune-brain pathways for mechanistic studies in animal models and in vitro systems, future studies will investigate the changes in the brain-immune-microbiome loop after specific treatments aimed at targeting overeating and altered ingestive behaviors in obesity. We will use automated processing pipelines, and large-scale and advanced bioinformatic analytic techniques, which allows to integrate information from multiple sources in order to achieve a systems biology-based understanding of obesity and sex-race related differences in the influence of psychosocial factors on the bidirectional interactions between the brain-gut microbiome axis.

Overall, we expect that the results will not only enhance our understanding of the pathophysiology of obesity but will also lead to the development of more effective and personalized treatments.

A combination of therapeutic approaches targeting different “nodes” of the system, and individualization of treatments based on differences in brain or gut microbial composition and function are required to provide greater clinical benefits.