Diversified pattern of the human colorectal cancer microbiome

Abstract

Background: The aim of this study is to expand existing knowledge about the CRC-associated microbiome among Han Chinese, and to further discover the variation pattern of the human CRC microbiome across all population.

Findings: Using pyrosequencing-based molecular monitoring of bacterial 16S rRNA gene from eight tumor/normal tissue pairs of eight Chinese CRC patients, we analyzed and characterized the basic features of the CRC-associated microbiome. Firstly, we discovered an increasing diversity among tumor-associated bacterial communities. Secondly, in 50% of Chinese CRC patients, we found a significant increase of Roseburia (P = 0.017), and a concurrent decrease of both Microbacterium (P = 0.009) and Anoxybacillus (P = 0.009) in tumor tissue.

Conclusions: We discovered a novel CRC microbiome pattern in Chinese. Both the over-represented Roseburia bacteria at tumor sites and the over-represented Microbacterium and Anoxybacillus bacteria away from tumor sites were both closely related in Chinese CRC patients. Across several populations reported in this study and previously, we observed both common and distinctive patterns of human CRC microbiome's association with a high-risk of CRC.

Figure 1

16S rRNA gene surveys reveal hierarchical partitioning of human tumor tissue-associated microbiomes. Bacterial communities were clustered using Principal Coordinate Analysis (PCoA) of the full-tree-based Unifrac matrix. Each point corresponds to a sample colored to indicate tumor or healthy status. Three principle components (PC1, PC2, and PC3) totally explained 43% of the variation. Sample name started with their corresponding studied patient number - S00X (X= 1, 2, 4, 5, 6, 7, 8, and 9), and the following tissue type (C stands for cancer tissue and H for matched adjacent health tissue).

Figure 2

Statistical comparisons of three dominant gut bacteria genera between tumor and normal tissues. A-C respectively showed two different variation patterns of each of three dominant bacteria genera (Roseburia, Microbacterium, and Anoxybacillus)–either the overrepresentation in tumor sites or in normal sites (separated by slash). Those tumor/normal tissue pairs with significant differentiation of dominant bacteria abundance were marked by a box. D, significantly increasing Roseburia in tumor tissue (mean, t-test) corresponding to four tumor/normal pairs from 50% of patients marked by a box (A); E, significant decreasing Microbacterium in tumor (median, Mann-Whitney rank sum test) corresponding to six tumor/normal pairs from 75% of patients marked by box (B); F, significant decreasing Anoxybacillus in tumor (median, Mann-Whitney rank sum test) corresponding to six tumor/normal pairs from 75% of patients marked by a box (C). Sample names started with their corresponding studied patient number - S00X (X= 1, 2, 4, 5, 6, 7, 8, and 9) and the following tissue type (C stands for cancer tissue and H for matched adjacent health tissue).