Genomic analysis of oral <i>Campylobacter concisus</i> strains identified a potential bacterial molecular marker associated with active Crohn’s disease

<i>Campylobacter concisus</i> is an oral bacterium that is associated with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC). <i>C. concisus</i> consists of two genomospecies (GS) and diverse strains. This study aimed to identify molecular markers to differentiate commensal and IBD-associated <i>C. concisus</i> strains. The genomes of 63 oral <i>C. concisus</i> strains isolated from patients with IBD and healthy controls were examined, of which 38 genomes were sequenced in this study. We identified a novel secreted enterotoxin B homologue, Csep1. The <i>csep1</i> gene was found in 56% of GS2 <i>C. concisus</i> strains, presented in the plasmid pICON or the chromosome. A six-nucleotide insertion at the position 654–659 bp in <i>csep1</i> (<i>csep1</i>-<i>6bpi</i>) was found. The presence of <i>csep1</i>-<i>6bpi</i> in oral <i>C. concisus</i> strains isolated from patients with active CD (47%, 7/15) was significantly higher than that in strains from healthy controls (0/29, <i>P</i> = 0.0002), and the prevalence of <i>csep1</i>-<i>6bpi</i> positive <i>C. concisus</i> strains was significantly higher in patients with active CD (67%, 4/6) as compared to healthy controls (0/23, <i>P</i> = 0.0006). Proteomics analysis detected the Csep1 protein. A <i>csep1</i> gene hot spot in the chromosome of different <i>C. concisus</i> strains was found. The pICON plasmid was only found in GS2 strains isolated from the two relapsed CD patients with small bowel complications. This study reports a <i>C. concisus</i> molecular marker (<i>csep1</i>-<i>6bpi</i>) that is associated with active CD.