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

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 data sets 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.

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

“…They always present alongside the normal colon cells in the tumor microenvironment. Therefore, a co‐culture study was performed to stimulate the intermediate development of CRC . The group had reported deregulation of acrogranin, insulin‐like growth factor binding protein 6 (IGFBP6) and vimentin which were suggested as inducer proteins for tumor progression .…”

“…Therefore, a co‐culture study was performed to stimulate the intermediate development of CRC . The group had reported deregulation of acrogranin, insulin‐like growth factor binding protein 6 (IGFBP6) and vimentin which were suggested as inducer proteins for tumor progression . In metastatic CRC, secretome studies had revealed more proteins that may be critical in metastatic events.…”

Clinically adaptable polymer enables simultaneous spatial analysis of colonic tissues and biofilms

“…Recently, increased abundance of Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli have been associated with human CRC [1][2][3] . These species are hypothesized to promote tumorigenesis and/or progression of CRC through up-regulation of oncogenes, modification of intestinal mucus, or damage to host DNA 2,4,5 . In addition to the mere presence or absence of putative carcinogenic bacteria in the gut, the spatial localization and physical interaction with host epithelial cells may be critically important.…”

“…In contrast, the inner, striated mucus layer of the colon is largely sterile in healthy hosts 6 . Perturbations of this tightly regulated spatial organization have been linked to both inflammatory bowel diseases (IBD) and CRC [12][13][14][15] . Mucosa-associated bacterial biofilms are defined as microbial aggregates embedded within a polymeric matrix of both host and bacterial origin that directly contacts epithelial cells 14,16 .…”

Commensal-derived succinate enhances tuft cell specification and suppresses ileal inflammation

“…Chloroplast and mitochondrial contaminants were detected and filtered using the RDP classifier with a confidence threshold of 80%. High-quality 16S rRNA sequences were assigned to a high-resolution taxonomic lineage using Resphera Insight(Drewes et al, 2017). Functional gene content was inferred using PICRUSt(Langille et al, 2013).…”