Ileal transcriptomic and mucosal microbiome features at resection are associated with postoperative recurrence in Crohn’s disease

Background and Aims : Crohn’s disease (CD) is a chronic, transmural inflammatory bowel disease. Half of patients undergo intestinal resection within 10 years after diagnosis, yet 70% develop endoscopic recurrence in the neoterminal ileum within the first postoperative year. We aimed to identify molecular features at the time of surgery in ileal tissue that are associated with later endoscopic recurrence. Methods: Matched host transcriptome and bacterial 16S rRNA gene amplicon sequencing were performed on the same FFPE ileal tissue section collected from 24 CD patients at the proximal resection margin. Endoscopic recurrence was assessed 6 months after surgery using the Rutgeerts score. Host transcriptome differences were quantified using differential expression, pathway enrichment, and gene co-expression network analysis. Microbial differences were assessed using diversity metrics and genus-level comparisons. Host–microbe associations were explored by correlating bacterial genera with host co-expression modules. Results: At the time of surgery, ileal tissue from patients with future endoscopic recurrence already exhibited significantly upregulated inflammatory and immune pathways, including interferon, TNF/NF-κB, IL-6, and complement signaling. Microbial community structure also differed between two groups. Several genera showed nominally significant differences in relative abundance, including Acinetobacter , Christensenellaceae_R-7_group , and Desulfovibrio . Exploratory host–microbe correlation analyses suggested linked changes between specific host modules and bacterial genera. Conclusions: Subclinical inflammatory activation and mucosal microbial differences in macroscopically normal proximal ileal tissue were associated with subsequent endoscopic postoperative recurrence in Crohn’s disease. Given the limited sample size, these findings are hypothesis-generating and suggest that molecular microbial alterations in macroscopically normal tissue may indicate recurrence risk.