Gut microbiota alterations associated with anxiety and depression in inflammatory bowel disease: a systematic review of prospective cohorts and randomized trials.

Background: Anxiety and depression are highly prevalent among patients with inflammatory bowel disease (IBD) and are closely associated with reduced quality of life and poor treatment adherence. The gut-brain axis has been proposed as a key mechanistic framework, with the gut microbiota playing a central role. However, findings from clinical studies remain inconsistent, and a comprehensive synthesis of the evidence is lacking. Objective: This systematic review aimed to integrate evidence from randomized controlled trials (RCTs) and prospective cohort studies to evaluate the associations between gut microbiota characteristics, microbiota-targeted interventions, and symptoms of anxiety and depression in patients with IBD. Methods: A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, EBSCOhost, and Scopus. The search covered records from database inception to October 17, 2025. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A descriptive synthesis approach was used to summarize the findings. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist. Results: Ten studies were included, comprising six prospective cohort studies and four RCTs. These studies included a total of 1,040 patients with IBD. Cohort studies consistently showed that anxiety and depressive symptoms were associated with reduced microbial α-diversity, enrichment of pro-inflammatory taxa, and depletion of short-chain fatty acid (SCFA)-producing bacteria. These associations persisted after adjustment for inflammatory markers. They were also observed when analyses were restricted to patients in remission. This suggests that the associations may not be fully explained by disease activity. Evidence from RCTs showed that microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, modulated microbial composition and reduced anxiety and depression scores. Studies combining psychological interventions with microbiota profiling also suggested potential effects on gut microbial composition. However, the findings remain heterogeneous. Conclusion: Current evidence supports a close and potentially bidirectional association between gut microbiota dysbiosis and anxiety and depression in patients with IBD. Both microbiota-targeted interventions and psychological therapies may represent promising strategies for managing psychological comorbidities in IBD. Future large-scale, standardized longitudinal studies and randomized controlled trials are warranted to clarify directionality, test causal hypotheses, and develop personalized intervention approaches. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251166542.