Bidirectional brain–gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis

Objective: The role of the brain–gut axis is of increasing interest in IBD, as the link between common mental disorders and GI inflammation may be bidirectional. We performed a systematic review examining these issues. Design: We searched EMBASE Classic and EMBASE, Medline, and APA PsychInfo (to 11 July 2021) for longitudinal follow-up studies examining effect of symptoms of anxiety or depression on subsequent adverse outcomes in IBD, or effect of active IBD on subsequent development of symptoms of anxiety or depression. We pooled relative risks (RRs) and HRs with 95% CIs for adverse outcomes (flare, escalation of therapy, hospitalisation, emergency department attendance, surgery or a composite of any of these) according to presence of symptoms of anxiety or depression at baseline, or RRs and HRs with 95% CIs for new onset of symptoms of anxiety or depression according to presence of active IBD at baseline. Results: We included 12 separate studies, recruiting 9192 patients. All 12 studies examined brain-to-gut effects. Anxiety at baseline was associated with significantly higher risks of escalation of therapy (RR=1.68; 95% CI 1.18 to 2.40), hospitalisation (RR=1.72; 95% CI 1.01 to 2.95), emergency department attendance (RR=1.30; 95% CI 1.21 to 1.39), or a composite of any adverse outcome. Depression at baseline was associated with higher risks of flare (RR=1.60; 95% CI 1.21 to 2.12), escalation of therapy (RR=1.41; 95% CI 1.08 to 1.84), hospitalisation (RR=1.35; 95% CI 1.17 to 1.57), emergency department attendance (RR=1.38; 95% CI 1.22 to 1.56), surgery (RR=1.63; 95% CI 1.19 to 2.22) or a composite of any of these. Three studies examined gut-to-brain effects. Active disease at baseline was associated with future development of anxiety or depression (RR=2.24; 95% CI 1.25 to 4.01 and RR=1.49; 95% CI 1.11 to 1.98, respectively). Conclusion: Bidirectional effects of the brain–gut axis are present in IBD and may influence both the natural history of the disease and psychological health