Siblings of patients with Crohn’s disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities

Objective: Siblings of patients with Crohn’s disease (CD) have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown. Objective: To determine the existence of mucosal dysbiosis in siblings of CD patients using 454 pyrosequencing and to comprehensively characterise, and determine the influence of genotypic and phenotypic factors, on that dysbiosis. Design: Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypic risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. Results: Core microbiota of both CD patients and healthy siblings were significantly less diverse than controls. Metacommunity profiling (Bray-Curtis (SBC) index) showed the sibling core microbial composition to be more similar to CD (SBC=0.70) than to HC, whereas the sibling rare microbiota was more similar to HC (SBC=0.42). Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD-risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Conclusions: Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at-risk of CD implicates microbiological processes in CD pathogenesis