Neural Circuit Mechanism of Inflammatory Bowel Disease Combined With Depression (NCMOIBDCWD)

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

The goal of this observational study is to understand the effects of gut microbiota dysbiosis treatment in patients with inflammatory bowel disease (IBD) combined with depression. The main question it aims to answer is:

Does fecal microbiota transplantation (FMT) improve depression symptoms in IBD patients by altering GABA levels in the medial prefrontal cortex?

Participants already undergoing fecal microbiota transplantation (FMT) as part of their regular medical care for IBD and comorbid depression will undergo regular assessments of GABA levels, gut microbiota, and depression symptoms for the duration of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Radiation: Magnetic resonance imaging scanning; Drug: FMT Protocol

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Jun Wang, Doctor; Phone Number: +8618298366202; Email: wangj20@lzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The inflammatory bowel disease (IBD) combined with depression have increased psychological stress. Individuals with IBD often face prolonged physical discomfort and treatment challenges, which can lead to increased emotional burden and susceptibility to depression. IBD is a chronic condition requiring long-term management and treatment. These ongoing lifestyle changes and medical burdens may contribute to feelings of sadness and depression. In summary, depression is common among individuals with inflammatory bowel disease. It is important to monitor the mental health of patients during treatment and provide proactive psychological support and intervention when needed.

Description

Inclusion Criteria:

aged 18-65 years right-handed active disease (CDAI score ≥150, Mayo score >2).

Exclusion Criteria:

previous brain surgery those with severe and unstable physical diseases those with contraindications for MRI who cannot tolerate long-duration MRI examinations.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CD; Crohn's disease	Radiation: Magnetic resonance imaging scanning; Perform brain diffusion imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging scans on all individuals; Drug: FMT Protocol; Treatment of disease groups (UC and CD) using prepared fecal microbiota transplantation solution
UC; ulcerative colitis	Radiation: Magnetic resonance imaging scanning; Perform brain diffusion imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging scans on all individuals; Drug: FMT Protocol; Treatment of disease groups (UC and CD) using prepared fecal microbiota transplantation solution
HC; healthy controls	Radiation: Magnetic resonance imaging scanning; Perform brain diffusion imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging scans on all individuals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic resonance spectroscopy	Changes in GABA content in the prefrontal lobe of the brain	1 week before and 1 week after FMT
Magnetic resonance spectroscopy	Changes in alpha diversity and differential abundance of gut microbiota	1 week before and 1 week after FMT

Collaborators and Investigators

• Sponsor: LanZhou University
• Investigators: Study Chair: Jun Wang, Doctor, The Second Hospital & Clinical Medical School, Lanzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: June 18, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 23, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 2024A-255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the data collection is completed, the collected gut microbiota data will be shared
• IPD Sharing Time Frame: Around December 31, 2026
• IPD Sharing Access Criteria: Email the corresponding author with reasonable reasons for inquiry
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No