Skype interview with Cindy Sears and Julia Drewes from John Hopkins University School of Medicine.

The link between colorectal cancer and microbiome dysbiosis has been suggested for a while now, but it's been difficult to draw concrete conclusions from experimental results. Work by a team of scientists from John Hopkins University School of Medicine in Baltimore published a study in NPJ Biofilms and Microbiomes today that hopefully gets us closer to some answers.

The team led by Cindy Sears studied a cohort of patients from Malaysia, as well as revisiting previously published studies with a new data analysis pipeline. They found that across all the patient groups, colorectal cancer cases were associated with invasive biofilms. This finding is important because it provides a clear hypothesis for how shifts in the microbiome can cause cancer. 

Another surprising finding from the study was that colorectal cancer samples were enriched for oral pathogens. The reason is unclear but Sears is excited by the result. She hopes that it may be possible to find markers in the oral microbiome that could help predict colorectal cancer. This would a huge boost for patient care, especially in countries where colonoscopies are not routine and where early detection and treatment will inevitably save lives.

Abstract

Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences in analysis methodologies. Complementing these taxonomic studies is the newly recognized phenomenon that bacterial organization into biofilm structures in the mucus layer of the gut is a consistent feature of right-sided (proximal), but not left-sided (distal) colorectal cancer. In the present study, we performed 16S rRNA gene amplicon sequencing and biofilm quantification in a new cohort of patients from Malaysia, followed by a meta analysis of eleven additional publicly available datasets on stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution analytical tool for species-level characterization. Results from the Malaysian cohort and the expanded meta-analysis confirm that CRC tissues are enriched for invasive biofilms (particularly on right-sided tumors), a symbiont with capacity for tumorigenesis (Bacteroides fragilis), and oral pathogens including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis. Considered in aggregate, species from the Human Oral Microbiome Database are highly enriched in CRC. Although no detected microbial feature was universally present, their substantial overlap and combined prevalence supports a role for the gut microbiota in a significant percentage (>80%) of CRC cases.

Reference

High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

Julia L. Drewes, James R. White, Christine M. Dejea, Payam Fathi, Thevambiga Iyadorai, Jamuna Vadivelu, April C. Roslani, Elizabeth C. Wick, Emmanuel F. Mongodin, Mun Fai Loke, Kumar Thulasi, Han Ming Gan, Khean Lee Goh, Hoong Yin Chong, Sandip Kumar, Jane W. Wanyiri & Cynthia L. Sears

npj Biofilms and Microbiomes 3, Article number: 34 (2017)

doi:10.1038/s41522-017-0040-3