Abstract 4414: Distinct taxonomic, metagenomic and metabolomic profiles from a comprehensive gut flora analysis in healthy and colon adenoma African Americans

Abstract

Abstract Background: Gut flora has long been suspected to play a role in colorectal cancer (CRC) pathogenesis. Elegant experiments have substantiated such claims with the use of single pathogenic bacteria in germ free colon cancer mouse models. Here we run a comprehensive taxonomic, metagenomic and metabolomics analysis of stool samples from healthy and colon adenoma African American (AA) patients to define further this role. Patients & Methods: DNA extracts from stool samples of 6 healthy and 6 colon adenoma patients were used for the taxonomic and metagenomic analysis. The sequencing was done using a 454 pyrosequencer and the generated data was processed using informatics pipeline for phylogenetic bacterial affiliation and for bacterial functions assignment. For the metabolomics analysis, 10 fecal water extracts from healthy individuals and 10 from colon adenoma patients were analysed for their metabolites’ contents using NMR spectrometry. Results: The analysis of 16S-rDNA sequences revealed the existence of 22 groups of bacteria. A phylogenetic clustering revealed colon adenoma cases clustering together. Most predominant groups in both sets of samples were Clostridia and Bacteroides. No Lactobacilli or Bifidobacteria (good bacteria) were detected. The synergistetes_Dynergistia group -involved in gastrointestinal infections and Firmicutes phylum: Firmicutes group - involved in energy resorption and obesity were 20 and 10 folds more prevalent in adenoma patients, respectively. Bacteria TM7 group that contain active agents in IBD was 5 folds more represented in the control compared to the adenoma group. The metagenomic experiment have led to the generation of about 100,000 reads per sample, 80% of which were successfully annotated. Among the annotated functions, many were differentially present in the colon adenoma compared to healthy individuals. The metabolomics analysis led to a strong clustering of the adenoma samples metabolomes further consolidating the role of bacteria and their metabolites in colon cancer pathology. Conclusion: Our taxonomic, metagenomic and metabolomics analysis have led the presence of clear differential profiles in colon adenoma patients vs. healthy persons. Lack of detection of “good bacteria” (Lactobacilli and Bifidobacteria) in this study defines already a first level of intervention in this high risk CRC population. A comprehensive analysis of all the results is underway to bridge the Taxo, Meta and metabolomics data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4414. doi:1538-7445.AM2012-4414