Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases

By D. Frank, C. Robertson, C. M. Hamm, Zegbeh Z. Kpadeh, Tianyi Zhang, Hongyan Chen, Wei Zhu, R. Sartor, E. Boedeker, N. Harpaz and 2 more. Inflammatory Bowel Diseases, 2010

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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 ATG16L1T300A 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 (NOD2R = at least one risk allele, NOD2NR = no risk alleles); 3) ATG16L1T300A genotype (ATG16L1R/R, ATG16L1R/NR, ATG16L1NR/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;)

Subfields: Genetics, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bc3fbd359a3dbe8cb4e25db651172f1caea286b4

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Citations in the corpus

The gut microbiota and inflammatory bowel disease (2014, unknown): “Furthermore, it was reported that the genetic status of NOD2 and ATG18L genes, which are two major CD susceptibility genes, was associated with alteration of the gut microbiota [28].”
Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome (2019, result): “The same results have been validated in recent human studies, supporting the presence of NOD2 risk alleles in correlation with a shift of microbial ecology composition in IBD patients’ colons [182,183].”
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment (2012, result): “Similarity among microbiome compositions in disease subtypes reflects those previously observed [34,35], with ileal CD (iCD) representing a strong outgroup, UC a generally less-extreme microbial phenotype (less dissimilar from healthy subjects), and non-iCD a broad distribution of microbiome configu”
Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis (2013, background): “, 2011; Human Microbiome Project Consortium, 2012) have characterized the composition and diversity of the healthy gut microbiome, and disease-associated studies revealed correlations between taxonomic abundance and some clinical phenotypes (Frank et al., 2011; Morgan et al., 2012; Qin et al., 2012)”
Human genetics shape the gut microbiome. (2014, unknown): “, 2011),andstudiescomparingmicrobiotas between human subjects differing at specific genetic loci have shown gene-microbiota interactions (Frank et al., 2011; Khachatryan et al., 2008; Rausch et al., 2011; Rehman et al., 2011; Wacklin et al., 2011).”
Metal Oxide Nanoparticles Induce Minimal Phenotypic Changes in a Model Colon Gut Microbiota (2015, unknown): “…of the gut microbiota is so prominent in human health that researchers have found links between gut microbes and numerous diseases (Ba¨ckhed et al. , 2004; Ley et al. , 2005, 2006; Manichanh et al. , 2006; Frank et al. , 2007, 2011; Lepage et al. , 2011; Mondot et al. , 2011; Hsiao et al. , 2013).”