Uncovering the Dynamics of Mucosa-Associated Microbiota in Postoperative Recurrence of Crohn’s Disease

BACKGROUND & AIMS: About 50% to 75% of patients with Crohn's disease (CD) need bowel resection. Postoperative recurrence of CD is frequent. Here, we investigate the evolution of the mucosa-associated microbiota along the Rutgeerts score measuring endoscopic recurrence after surgery. METHODS: We used 16S ribosomal RNA and ITS2 sequencing to profile the mucosa-associated microbiota of biopsies from patients with CD at the time of surgery (M0, n = 139) and later, at the time of endoscopic assessment of recurrence (M6, n = 125). RESULTS: Although the effect of surgery and recurrence were moderate on the overall microbiota composition, we identified specific microbial signatures displaying differential relative abundance when accounting for clinical covariates. The relative abundance of certain species, notably a decrease of Faecalibacterium prausnitzii, or increase of Akkermansia muciniphila, was differentially associated with a whole range of Rutgeerts score or with more specific scores characterizing the inflammation of the anastomosis or the ileum. In addition, machine learning performances were impacted by the consideration of the Rutgeerts score as a multilevel prediction instead of a binary classification, further confirming the need to consider its full range. Finally, we investigated the community dynamics, which highlighted a denser network organization after surgery and in the absence of recurrence, along with changes in keystone species. CONCLUSIONS: Altogether, these results provide further understanding of the effects of ileal resection in patients with CD and show that disease recurrence is a dynamic process characterized by several waves of changes in the microbiota composition.