Risk of Colorectal Cancer Linked to Composition of the Gut Microbiome

The composition of the community of bacteria living in the digestive tract has been linked to the risk of developing colorectal cancer (CRC).

Colorectal cancer is diagnosed in about 143,000 Americans annually with nearly 51,000 fatalities, making it second only to lung cancer in the number of deaths caused each year. However, it is not well understood why colorectal cancer develops.

Investigators at the New York University School of Medicine (NY, USA) tested the hypothesis that an altered community of gut microbes was associated with risk of developing CRC. To this end, they compared the DNA composition of intestinal microbes in the stool samples of 47 CRC patients and 94 healthy volunteers.

16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by Roche (Basel, Switzerland) 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME protocol.

QIIME, which stands for Quantitative Insights into Microbial Ecology, is an open source software package for comparison and analysis of microbial communities, primarily based on high-throughput amplicon sequencing data generated on a variety of platforms, but also supporting analysis of other types of data. QIIME chaperones users from their raw sequencing output through initial analyses such as OTU (operational taxonomic unit) picking, taxonomic assignment, and construction of phylogenetic trees from representative sequences of OTUs, and through downstream statistical analysis, visualization, and production of publication-quality graphics. QIIME has been applied to studies based on billions of sequences from thousands of samples.

Taxonomic differences identified in this study were confirmed by quantitative polymerase chain reaction (qPCR) and adjusted for false discovery rate. Data from 794,217 16S rRNA gene sequences revealed that CRC case subjects had decreased overall microbial community diversity. In taxonomy-based analyses, lower relative abundance of Clostridia and increased carriage of Fusobacterium and Porphyromonas were found in case subjects compared with control subjects. Clostridia include some bacterial family members that ferment dietary fiber to butyrate, which is a major colonic metabolite that may inhibit inflammation and carcinogenesis in the colon, while Fusobacterium and Porphyromonas are related to inflammation in the mouth and gastrointestinal track.

"Our findings are important because identification of these microbes may open the door for colorectal cancer prevention and treatment," said first author Dr. Jiyoung Ahn, assistant professor of population health at the New York University School of Medicine. "Our next step is to study how diet and lifestyle factors modulate these gut bacteria associated with colorectal cancer. This may lead to ways to prevent this disease."

The paper was published in the December 6, 2013, online edition of the Journal of the [US] National Cancer Institute.

Related Links:
New York University School of Medicine
Roche
QIIME