Invasive Potential of Gut Mucosa-derived Fusobacterium nucleatum Positively Correlates with IBD Status of the Host

Background: Fusobacterium nucleatum is a heterogeneous oral pathogen that is also a common resident of the human gut mucosa. Given that some strains of F. nucleatum are known to be invasive and proinflammatory in the oral mucosa, we compared strains isolated from patients with inflammatory bowel disease (IBD) with strains isolated from healthy controls to determine I) whether this species was more commonly associated with IBD patients; and 2) whether gut-derived F. nucleatum strains from IBD patients showed an increased capacity for invasion. Methods: Biopsy material was obtained from 56 adult patients undergoing colonoscopy for colon cancer screening purposes or assessment of irritable bowel syndrome status (34 patients), or to assess for presence of gastrointestinal disease (i.e.. IBD or indeterminate colitis, 22 patients). We enumerated Fusobacterium spp. strains isolated from human gut biopsy material in a blinded fashion, and then compared the virulence potential of a subset of F. micleatum strains using an invasion assay in a Caco-2 model system. Results: Fusobacterium spp. were isolated from 63.6% of patients with gastrointestinal disease compared to 26.5% of healthy controls (P = 0.01). In total, 69% of all Fusobacterium spp. recovered from patients were identified as F. nucleatum. F. nucleation strains originating from inflamed biopsy tissue from IBD patients were significantly more invasive in a Caco-2 cell invasion assay than strains that were isolated from healthy tissue from either IBD patients or control patients (P < 0.05 to 0.001). Conclusions: This study indicates that colonization of the intestinal mucosa by highly invasive strains of F. nucleation may be a useful biomarker for gastrointestinal disease.