From preclinical phase of Crohn's disease to postoperative recurrence: shared mechanisms and potential interventions

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with high risk of surgery. Despite advances in medical treatment, of those patients who undergo ileocolonic resections, up to 70% of patients experience postoperative recurrence (POR) within 1 year of surgery. This underscores the need for a better understanding of the pathogenesis of POR. We hypothesise that the transient 'disease-free' state following surgical resection biologically mirrors the earliest preclinical stages of new-onset CD and that shared biomarkers across preclinical and postoperative settings reflect common pathogenic pathways. Identifying these shared signatures may offer a unique opportunity to elucidate mechanisms underlying both disease initiation and recurrence and to inform strategies aimed at prevention of new onset CD as well as POR. In this review, we synthesise insights from recent biomarker and multiomics studies spanning preclinical and postoperative CD cohorts. We highlight predictive biomarkers shared across CD onset and POR, including genetic variants, immune mediators such as CXCL9 and interleukin 6, microbial signatures involving Faecalibacterium and Ruminococcus and markers of gut barrier dysfunction and systemic inflammation. We also discuss emerging omics approaches including glycomics, urine metabolomics and high-dimensional immunophenotyping that may further refine risk stratification, capture pathogenic heterogeneity and provide mechanistic insight into host-microbe-immune interactions. Finally, we outline potential intervention strategies targeting these shared pathways and propose that the postoperative setting could be a pragmatic human model to test biomarker-guided preventive approaches applicable across the CD spectrum.