Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease? a systematic review and meta-analysis

Background: Psychoneuroimmunological mechanisms and the gut-brain axis appear relevant to disease activity and progression in Inflammatory Bowel Disease (IBD). A recent review showed no effect of psychological therapies on self-reported disease activity in IBD. This meta-analysis aims to establish whether interventions targeting mood outcomes (e.g., depression, anxiety and stress) impact inflammation levels in IBD and possible moderators of these effects. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched five electronic databases and included randomised controlled trials where interventions targeted mood and assessed inflammatory outcomes pre- and post-intervention in adults with IBD. Independent reviewers screened studies, extracted data, and assessed methodological quality. Data were pooled to estimate standardised mean differences (SMDs) with 95% Confidence Intervals (CIs). A random-effects robust variance estimation accounted for studies measuring multiple biomarkers. Intervention type, mood as a primary or secondary outcome, effect on mood outcomes and IBD subtype were investigated as treatment effect moderators. Where there were sufficient biomarkers, individual meta-analyses were run (Pre-registration PROSPERO: CRD42023389401). Findings: 28 RCTs involving 1789 participants met inclusion criteria. Interventions demonstrated small, statistically significant effects on biomarkers (−0.35, 95% CI: −0.48, −0.22, p < 0.001) and medium effects on mood outcomes (−0.50, 95% CI: −0.73, −0.27, p < 0.001), without evidence of substantive heterogeneity or publication bias. Individual analyses showed small effects for improved faecal calprotectin (−0.19, 95% CI: −0.34, −0.03, p = 0.018) and C-Reactive Protein (−0.29, 95% CI: −0.47, −0.10, p = 0.002). Effect sizes were larger for psychological therapy interventions (compared with exercise or antidepressants) and when there was an effect (SMD ≥0.2) on mood. Interpretation: Treatments which address mood outcomes have beneficial effects on generic inflammation as well as disease-specific biomarkers (faecal calprotectin and C-Reactive Protein). Psychological interventions and interventions with larger treatment effects on mood accentuated the effect on biomarkers. More research is required to understand the biological or behavioural mechanisms underlying this effect. Funding: The Medical Research Council and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.