セッション情報 Host-microbial Interaction and Immunology in IBD a. Basic Aspects

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IF3a-2 Disease Phenotype and Genotype in Intestinal Microbiota of Inflammatory Bowel Diseases

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抄録 The aim of this study was to interrogate how host-microbial interactions are perturbed in inflammatorybowel diseases (IBD) by integrating human clinicalgenotypemRNA microarrayand 16S rRNA sequencedata collected on subj ects wi廿1 ileal Crohn’s diseaseulcerative colitis or c6ntrol patients without IBD. Bac-terial 16S ribosomal RNA (rRNA) sequencing was conducted on macroscopically disease-unaffected ilealbiopsies collected from 52 ileal CD58 ulcerative colitis an d 60 control patients without・IBD undergoing in-itial surgical resection. These subj ects also were genotyped for the three major NOD2 risk alleles (Leu1007fsR708WG908R) and the ATG16Ll risk allele (T300A). Whole human genome n tf. (NA expressionprofiling was conducted in parallel for a sub set of the subj ects・ (n = 84) using Agilent rnicroarrays.IBD phenotypeClostridia difficile and NOD2 genotype were selected as associated (FDR f!{O.05) withshifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associ-ated with shifts in the relative frequency of the・ C. coccoides-E. rectales group. IBD phenotypesmokingand IBD medications were selected as associated with shits in the relative frequency of F. prausnitzii spp.integration of microbiome and whole human genome gene expression profiling datasets revealed severalclusters of human genes that were differentially expressed in correlation with the abundances of particu-1’ar microbial groups. These results support the hypotheses that 1) host mucosai Paneth cell and xenobioticmetabolism genes play an important role in host microbial interactions and 2) the effects of genetic and en-vironmental factors on IBD are mediated at least in part by the enteric microbiota.
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