Microbiota recolonization after ileocecal resection differs in Crohn's disease patients developing postoperative recurrence

Dysbiosis of the intestinal microbiota is implicated in Crohn's disease (CD) and may play an important role in triggering postoperative disease recurrence (POR).We hypothesized that the fecal and mucosal microbial recolonization process after leocecal resection differs between patients developing recurrence and patients emaining in remission, and further aimed to identify the predictive value of recurrence-related microbiota.MethodsMucosal and/or fecal samples from 121 CD patients undergoing ileocecal resection with ileocolonic anastomosis were prospectively collected before and at multiple predefined time points after surgery. Mucosal ileal biopsies were also collected from 39 healthy controls. POR at month 6 was defined by a Rutgeerts score =i2b. The microbiota was evaluated by 16S rDNA sequencing using an Illumina MiSeq platform. Prediction analyses was performed using two independent machine learning models.ResultsThe mucosa-associated microbiota of CD patients undergoing a resection harbored a reduced relative abundance of many genera belonging to the Lachnospiraceae (FDR<0.01) and Ruminococcaceae (FDR<0.01) families, and an increased abundance of Proteobacteria (FDR=0.009) and Akkermansia spp. (FDR=0.02) compared to healthy controls.Following resection, all patients showed a mucosal enrichment of Lachnospiraceae (FDR<0.001). In recurrence patients, also Fusobacteriaceae (FDR<0.001), Moraxellaceae (FDR=0.07), Promicromonosporaceae (FDR=0.07) and Erysipelotrichaceae (FDR=0.07) increased compared to baseline. Patients without recurrence showed a decrease of Streptococcaceae (FDR=0.003) and Actinomycineae (FDR=0.06).At month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes (FDR=0.04) and Fusobacteria (FDR=0.04) compared to the remission patients. These results were partly reflected in the fecal cohort. Prediction analyses based on the mucosa-associated microbiota revealed good discriminative power to predict recurrence, which was superior to clinical risk factors.ConclusionThe mucosa-associated microbiota in patients with CD who need an ileocecal resection is imbalanced, and characterised by a depletion of butyrate-producing species and enrichment of Proteobacteria and Akkermansia spp. The recolonization after ileocecal resection between recurrence and non-recurrence patients revealed substantial differences in the microbiota composition of particular species involved in biofilm formation, with Fusobacteria as the most prominent player. These results suggest that these bacteria involved in the early recolonization process are also involved in early POR, and might be a promising strategy in the development of a preventative treatment of recurrence.