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PMID: 22719818 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

PloS one ·Vol. 7 ·No. 6 ·2012-00-00 ·Pages e26284

Li E, Hamm CM, Gulati AS, Sartor RB, Chen H, Wu X, Zhang T, Rohlf FJ, Zhu W, Gu C, Robertson CE, Pace NR, Boedeker EC, Harpaz N, Yuan J, Weinstock GM, Sodergren E, Frank DN

Abstract

We tested the hypothesis that Crohn's disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota.

MeSH Terms
Clostridioides difficile/isolation & purification Genotype Humans Ileum/microbiology Inflammatory Bowel Diseases/microbiology Nod2 Signaling Adaptor Protein/genetics Phenotype Polymerase Chain Reaction Polymorphism, Single Nucleotide RNA, Ribosomal, 16S/genetics
Chemicals
NOD2 protein, human Nod2 Signaling Adaptor Protein RNA, Ribosomal, 16S
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Li Ellen
Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America. ellen.li@stonybrook.edu
Hamm Christina M
Gulati Ajay S
Sartor R Balfour
Chen Hongyan
Wu Xiao
Zhang Tianyi
Rohlf F James
Zhu Wei
Gu Chi
Robertson Charles E
Pace Norman R
Boedeker Edgar C
Harpaz Noam
Yuan Jeffrey
Weinstock George M
Sodergren Erica
Frank Daniel N
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0026284
Email
ellen.li@stonybrook.edu
Published
2012-00-00
Epub
2012-00-13
Pages
e26284
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3374607
Subset
IM
Grants
NHGRI NIH HHS · R21 HG005964 · United States
NHGRI NIH HHS · NIH R21HG005964 · United States
NIDDK NIH HHS · P30 DK52574 · United States
NIDDK NIH HHS · UH2 DK083994 · United States
NIDDK NIH HHS · P30 DK052574 · United States
NIDDK NIH HHS · UH2DK083994 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0026284 PMC Full Text View journal details
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