Study on the Neural Circuit Mechanism of Regulating GABA by Gut Microbiota in Inflammatory Bowel Disease Combined With Depression

The high incidence of inflammatory bowel disease (IBD) combined with depression increases the risk of disease recurrence and treatment failure. Previous research by our team has found a positive correlation between decreased levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the medial prefrontal cortex of IBD patients and the severity of depression. However, the underlying pathological mechanisms remain unknown. Prior studies have suggested that GABA regulates activity within neural circuits in the brain, and the levels of GABA in the brain are influenced by the gut microbiota. Based on this premise, our study aims to treat gut microbiota dysbiosis in IBD patients with comorbid depression using fecal microbiota transplantation (FMT). Our team will analyze the correlation between changes in GABA levels in the medial prefrontal cortex and gut microbiota using techniques such as metagenomics, metabolomics, and magnetic resonance spectroscopy imaging. Additionally, resting-state functional magnetic resonance imaging (fMRI) is used to perform dynamic causal modeling of the neural circuit in the brain to elucidate the regulatory mechanism of GABA level changes on these circuits. Finally, the investigators will validate the research findings using a dextran sulfate sodium (DSS)-induced colitis mouse model to explore the neurochemical mechanisms underlying IBD comorbid with depression. The results of this study will not only provide a deeper understanding of the regulatory role of changes in brain GABA levels on neural circuits but also offer a theoretical basis for the use of fecal microbiota transplantation in treating gut microbiota dysbiosis in IBD patients and prevent complications such as depression.