TY - JOUR
T1 - Siblings of patients with Crohn's disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities
AU - Hedin, Charlotte
AU - Van Der Gast, Christopher J.
AU - Rogers, Geraint B.
AU - Cuthbertson, Leah
AU - McCartney, Sara
AU - Stagg, Andrew J.
AU - Lindsay, James O.
AU - Whelan, Kevin
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Objective: To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with 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. 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. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. Results: Core microbiota of both patients with CD and healthy siblings was 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 healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (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.
AB - Objective: To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with 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. 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. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. Results: Core microbiota of both patients with CD and healthy siblings was 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 healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (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.
UR - http://www.scopus.com/inward/record.url?scp=84930399071&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2014-308896
DO - 10.1136/gutjnl-2014-308896
M3 - Article
AN - SCOPUS:84930399071
SN - 0017-5749
VL - 65
SP - 944
EP - 953
JO - Gut
JF - Gut
IS - 6
ER -