Oral Microbiome of Crohn's Disease Patients With and Without Oral Manifestations

Abstract

BACKGROUND AND AIMS: Microbiome dysbiosis is associated with inflammatory destruction in Crohn's Disease (CD). Although gut microbiome dysbiosis is well-established in CD, the oral microbiome is comparatively under-studied. This study aims to characterize the oral microbiome of CD patients with/without oral manifestations. METHODS: Patients with CD were recruited with age, gender and race-matched controls. Potential confounders such as dental caries and periodontal condition were recorded. Oral microbiome was collected using saliva samples. Microbial DNA extracted and sequenced using shotgun sequencing. Metagenomic taxonomic and functional profiles were generated and analyzed. RESULTS: The study recruited 41 with CD and 24 healthy controls. Within the CD subjects, 39.0% had oral manifestations with the majority presenting with cobblestoning and/or oral ulcers. Principal coordinate analysis demonstrated distinct oral microbiome profiles between subjects with and without CD, with 4 key variables responsible for overall oral microbiome variance: 1) Diagnosis of CD, 2) Concomitant use of steroids, 3) Concomitant use of Azathioprine, and 4) Presence of oral ulcers. Thirty-two significant differentially abundant microbial species were identified, with the majority associated with the diagnosis of CD. A predictive model based on differences in the oral microbiome found that the oral microbiome has strong discriminatory function to distinguish subjects with and without CD (AUROC 0.84). Functional analysis found increased representation of microbial enzymes (n=5) in the butyrate pathway was positively associated with the presence of oral ulcers. CONCLUSIONS: Oral microbiome can aid in the diagnosis of CD and its composition was associated with oral manifestations.