Human gut microbiome and risk for colorectal cancer

Abstract

We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.

Figures

Figure 1.

Human gut microbiome in relation to colorectal cancer case-control status. A) Shannon diversity index in 47 colorectal cancer case subjects and 94 control subjects. B) Evenness index in 47 colorectal cancer case subjects and 94 control subjects. Rarefaction curves were estimated by bootstrapping of 500 random samples at 500 sequence increments. Alpha diversity (Shannon’s diversity and evenness indices) differences between case and control subjects were compared with t tests with Monte Carlo permutations using compare_alpha_diversity.py, a built-in function in the QIIME pipeline. C) Cladogram representation of gut microbiome taxa associated with colorectal cancer. Red indicates taxa enriched in colorectal cancer case subjects, and blue indicates taxa enriched in control subjects. Only taxa with nominal P less than .05 based on χ2 test (dichotomized) or Wilcoxon test (continuous) are labeled. The tests were two-sided. Figure was constructed using data presented in in Table 1.