OC-051 Microbial, phenotypic and genetic markers of risk: aspects of crohn's disease that are shared by unaffected siblings: Abstract OC-051 Table 1

Abstract

Introduction: Siblings of Crohn's disease (CD) patients have elevated risk of developing disease which may manifest as raised faecal calprotectin (FC) and increased intestinal permeability. Other features of CD that reflect the at-risk state and their interactions are not well described. Aim Identify key facets of the at-risk state and establish their relationships. Methods: Faecal samples from 22 patients with quiescent CD, 21 siblings and 25 controls were analysed for FC (ELISA) and microbiota (quantitative PCR targeting bacterial 16S ribosomal RNA genes). Genotype RR at 72 known CD risk loci was determined by Illumina Immuno BeadChip, analysed with the REGENT R package. p Values from non-parametric analyses were Bonferroni corrected to adjust for multiple testing. Results: FC was elevated (>50 μg/g) in 21 (96%) patients, 8 (38%) siblings and 2 (8%) controls. Compared with controls, patients had reduced Bacteroidetes, clostridial cluster IV, Faecalibacterium prausnitzii, Ruminococci, Bifidobacterium adolescentis and Roseburia spp. (Abstract OC-051 table 1). Similarly, in siblings vs controls there was reduced cluster IV clostridia, (specifically F prausnitzii) and Roseburia spp. (Abstract OC-051 table 1). This dysbiosis was evident in siblings with normal FC. Siblings with elevated/high genotype RR (n=4) had normal FC but reduced Bacteroidetes vs controls, (9.2 vs 10.4 log10/g, p=0.007). Conclusion: In addition to enhanced genotypic risk and elevated FC, siblings share aspects of CD dysbiosis, in particular lower butyrate producing bacteria. Reduced Bacteroidetes comparable to that seen in patients, was only found in siblings with increased genotypic risk, raising the possibility of genetic determination. Sibling dysbiosis occurred independently from inflammation. Dysbiosis appears to be an early event in CD pathogenesis and may be an additional marker of CD risk.