Open AccessDisease phenotype and genotype are associated with shifts in intestinal‐associated microbiota in inflammatory bowel diseases
Author(s) -
Frank Daniel N.,
Robertson Charles E.,
Hamm Christina M.,
Kpadeh Zegbeh,
Zhang Tianyi,
Chen Hongyan,
Zhu Wei,
Sartor R. Balfour,
Boedeker Edgar C.,
Harpaz Noam,
Pace Norman R.,
Li Ellen
Publication year - 2011
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21339
Subject(s) - atg16l1 , nod2 , genotype , inflammatory bowel disease , biology , allele , ulcerative colitis , gut flora , genetics , immunology , disease , medicine , gene , innate immune system , immune system
Background: Abnormal host–microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal‐associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk alleles may be associated with these alterations. Methods: To test this hypothesis, we genotyped 178 specimens collected from 35 CD, 35 UC, and 54 control patients for the three major NOD2 risk alleles (Leu 1007fs, R702W, and G908R) and the ATG16L1 T300A risk allele, that had undergone previous 16S rRNA sequence analysis. Our statistical models incorporated the following independent variables: 1) disease phenotype (CD, UC, non‐IBD control); 2) NOD2 composite genotype ( NOD2 R = at least one risk allele, NOD2 NR = no risk alleles); 3) ATG16L1 T300A genotype ( ATG16L1 R/R , ATG16L1 R/NR , ATG16L1 NR/NR ); 4) patient age at time of surgery and all first‐order interactions. The dependent variable(s) were the relative frequencies of bacterial taxa classified by applying the RDP 2.1 classifier to previously reported 16S rRNA sequence data. Results: Disease phenotype, NOD2 composite genotype and ATG16L1 genotype were significantly associated with shifts in microbial compositions by nonparametric multivariate analysis of covariance (MANCOVA). Shifts in the relative frequencies of Faecalibacterium and Escherichia taxa were significantly associated with disease phenotype by nonparametric ANCOVA. Conclusions: These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal‐associated microbiota. (Inflamm Bowel Dis 2011;)