Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans

Abstract

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.

Gut microbiome development along the colorectal adenoma–carcinoma sequence

“…1b,e), while the a-diversities were not (Fig. 1c,f), consistent with previous 16S ribosomal RNA gene pyrosequencing analysis on adenoma and healthy controls 17 . The number of virulence genes according to the virulence factor database 18 also significantly differed among the groups (P ¼ 1.2e-5, Kruskal-Wallis test; Fig.…”

Utilizing “Omics” Tools to Study the Complex Gut Ecosystem

“…As an example, a recent study used 454 sequencing of 16S rRNA amplicons to compare the microbial community in punch biopsies taken from 33 subjects with colorectal adenomas and 38 control subjects [12]. In total, slightly more than half a million 16S rRNA sequences with an average length of just over 300 basepairs were generated from these 71 subjects.…”

“…We see that many of the taxa that are different between case and control are in the phyla Proteobacteria. By creating a visualization that merges phylogeny with canonical hypothesis testing, we are therefore able to begin to implicate specific groups of taxa in disease (see [12] for more information).…”

“…Putting this together-two orders of magnitude to detect a taxa at average 1 % abundance times three orders of magnitude variation in that taxa between people of different phenotypes times one order of magnitude technical variation in the number of sequences collected per sample-we see that it is not unreasonable to produce and analyze one million 16S sequences per sample. 1 Phylogenetic tree generated from Operational Taxonomic Units (OTUs) representing clusters of sequences with an average 97 % identity from a study of colorectal adenomas in humans [12]. Branches that are colored red represent taxa that are significantly different between cases and controls at a 10 % False Discovery Rate (see [12] for methodological details)…”

The Epidemiologic Evidence and Potential Biological Mechanisms for a Protective Effect of Dietary Fiber on the Risk of Colorectal Cancer

“…This question is now being addressed with molecular techniques; at present the only data show differences in the microbiome adherent to adenomas [65] and carcinomas [66,67], although this may have nothing to do with causation and may merely reflect changes in mucin layers in the tumors. It is not clear if luminal or mucosal bacteria (or both) are the important players in carcinogenesis.…”