Inflammatory bowel disease (IBD) is often comorbid with depressive disorder, and the development and progression of both conditions are closely related to the composition of gut microbiota and metabolites. However, studies investigating their comorbidity using microbiome and metabolomics approaches remain limited.

This study aims to investigate the diversity changes in the gut microbiome and metabolome of patients with comorbid IBD and depressive disorder through multi-omics approaches, to identify specific microbial and metabolic signatures associated with the comorbidity of these two conditions, and to provide a molecular basis for elucidating the underlying mechanisms.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that significantly impairs patients' quality of life. Depressive disorder is a common comorbidity in patients with IBD, and the coexistence of the two conditions can exacerbate disease burden and complicate treatment management. Increasing evidence suggests that both IBD and depressive disorder are closely related to alterations in the gut microbiome and metabolome; however, studies focusing on the comorbidity of these two conditions using multi-omics approaches remain limited.

This cross-sectional observational study aims to investigate the diversity and compositional changes of the gut microbiome and metabolome in patients with comorbid IBD and depressive disorder. Fecal, blood, and intestinal mucosal samples will be collected from three groups: (1) patients with IBD and comorbid depressive disorder, (2) patients with IBD without depressive disorder, and (3) control group. Through multi-omics analysis, the study seeks to identify specific microbial taxa and metabolites associated with the comorbidity of IBD and depressive disorder, uncover differential microbial and metabolic profiles among the three groups, and explore the potential molecular mechanisms underlying the interaction between intestinal inflammation and depressive symptoms. The findings are expected to provide a scientific basis for the development of novel diagnostic biomarkers and therapeutic strategies for IBD patients with comorbid depressive disorder.

Inclusion Criteria:

IBD with Depressive Disorder Group:

1. Patients diagnosed with inflammatory bowel disease (ICD-10 codes: K50-K51).
2. History of depressive disorder diagnosis or previous use of antidepressant medications.
3. Age ≥ 18 years.
4. Willingness to participate and provision of written informed consent.

IBD without Depressive Disorder Group:

1. Patients diagnosed with inflammatory bowel disease (ICD-10 codes: K50-K51).
2. No history of depressive disorder diagnosis
3. No previous use of antidepressant medications.
4. Age ≥ 18 years.
5. Willingness to participate and provision of written informed consent.

Control Group:

1. No history of inflammatory bowel disease, depressive disorder, or use of antidepressant medications.
2. No gastrointestinal symptoms (e.g., diarrhea, constipation, abdominal pain) within the past 3 months, and no history of gastrointestinal diseases.
3. Age ≥ 18 years.
4. Willingness to participate and provision of written informed consent.

Exclusion Criteria:

1. Presence of other major chronic diseases or infections (e.g., malignancy, hypertension, diabetes, coronary heart disease).
2. Use of antibiotics or probiotic supplements within the past 6 months.
3. Inability or difficulty in providing biological samples.
4. Missing essential patient information.

Patients with inflammatory bowel disease with or without comorbid depressive disorder, and control participants, recruited from the First Affiliated Hospital of Shandong First Medical University.