Genomic association of Campylobacter concisus for colonization advantages and virulence in children and adolescents with inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the intestinal microbiota, where oral microbes may benefit from resulting niches and colonize the intestine. We investigated Campylobacter (C.) concisus, an oral commensal and suspected intestinal pathogen in IBD, for genomic features facilitating intestinal colonization. We aimed to validate suggested virulence factors in IBD and to uncover patterns of propagation within and between hosts of C. concisus. We cultured C. concisus in a retrospective cohort of pediatric patients with IBD and with acute enteritis as diseased non-IBD controls from stool samples. In addition, in a prospective cohort of pediatric IBD patients we repeatedly collected saliva and stool samples for culturing. Whole genomes of C. concisus were compared for genomic similarity, virulence factors and antibiotic resistance genes dependent upon sample locations and disease groups. We also determined associations between genomic determinants and IBD phenotypes. The resulting 40 C. concisus genomes (19 saliva IBD, 13 stool IBD, 8 stool non-IBD) showed a high genomic diversity within and between sample locations and disease groups. We found multiple colonization scenarios in regards to sample locations, timing and genomic diversity in the IBD cohort. C. concisus IBD genomes were evenly distributed between the two genome species GS1 and GS2 and we found no difference between disease groups with regards to the tested virulence factors. Interestingly, only C. concisus IBD genomes harbored a gyrA_T86I mutation with phenotypically confirmed ciprofloxacin resistance independent of previous ciprofloxacin exposure. We found no indication of IBD phenotypes supporting intestinal colonization besides clinical active disease. All C. concisus strains contained genes that enable nitrate utilization (napAGH), as an indicator of the ability to adapt their energy metabolism. Our data do not support a role of previously suggested IBD associated virulence factors. Instead, they point to the possibility that C. concisus adapts to intestinal inflammation due to its genetic predisposition to alter its energy metabolism independent of IBD.