Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study.

Abstract

Crohn's disease pathogenesis involves alterations in the gut microbiota. We characterized the mucosa-associated microbiota at the time of surgical resection and 6 months later to identify bacterial profiles associated with recurrence and remission. Tissue samples were collected from surgical resection specimens in 12 Crohn's disease patients, and at 6 months postoperative colonoscopy from the neoterminal ileum and anastomosis. Endoscopic recurrence was assessed using the Rutgeerts score. Microbiota was characterized using microarray and 454 pyrosequencing. Longitudinal comparisons were made within patients, and cross-sectional comparisons made with colonoscopic biopsies from the terminal ileum and cecum of 10 healthy subjects. Microbiota of healthy subjects had high diversity and was dominated by the Firmicutes, Bacteroidetes, and Proteobacteria phyla. Biodiversity was lower in Crohn's disease patients at the time of surgery, increased after surgery, but still differed from healthy subjects. Crohn's disease patients with recurrent disease retained a microbiota favoring proteolytic-fueled fermentation and lactic acid-producing bacteria, including Enterococcus and Veillonella spp., while those maintaining remission demonstrated predominant saccharolytic Bacteroides, Prevotella, and Parabacteroides spp., and saccharolytic, butyrate-producing Firmicutes. In Crohn's disease, the mucosa-associated microbiota diversity is reduced at the time of surgery, but also differs between patients with different clinical outcomes at 6 months. These findings may provide prognostic information at the time of surgery, allowing identification of patients at increased risk of recurrence, and provide basis for a more targeted approach for therapeutic interventions after surgery.