Tumour-associated and non-tumour-associated microbiota in colorectal cancer

Abstract

ObjectiveA signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study.DesignWe prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR.ResultsThe microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes.ConclusionsCRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.

Race-specific differences in mucosal sulfidogenic bacteria modify colon cancer risk

“…Although this study supported an over expression of oral bacteria associated with CRC, it did not demonstrate over-representation of the fusobacterium on the cancer specimens. This study also corroborates previous evidence that microbial composition of proximal and distal cancers differ8 and that Pyramidobacter is enriched in proximal cancers and it provides tantalising evidence that young patients from high-risk ethnic cohorts have an associated dysbiosis. Bilophila, Parabacteroides, Odoribacter and an unknown genus of the Barnesiellaceae family were also associated with early onset CRC and the genus Acidaminococcus was associated with controls <50 suggesting that early onset CRC in AAs may also have its own dysbiotic state.…”

“…The over-representation of SRBs was also seen in off cancer biopsy sites when compared with cancer mucosa within the AA cohort. It has been previously established that the microbiota of patients with CRC differs from that of controls, and that these alterations are not restricted to the cancerous tissue 8. However, the group also reported clear reciprocal changes between AA and NHW in mean gene copy numbers of Desulfobacter, Desulfobulbus and Desulfotomaculum spp.…”

Tumour-associated and non-tumour-associated microbiota in colorectal cancer

“…The authors provide convincing data to illustrate that faecal microbiota does not reflect accurately the underlying mucosal microbiota in patients with colorectal cancer (CRC) 1. The authors also provide supporting evidence to illustrate that microbiota from sampled mucosa both on and off the cancer site is not significantly different.…”

“…We read with interest the elegant study published by Flemer et al 1 and commend the authors on their work. The authors provide convincing data to illustrate that faecal microbiota does not reflect accurately the underlying mucosal microbiota in patients with colorectal cancer (CRC) 1.…”

Biomarkers in Colorectal Cancer Screening

“…Gut bacterial composition in patients with CRC differed significantly from that in healthy patients. 36,37 Certain types of bacterial species, such as Fusobacterium, Bacteroides, Parvimonas, and Solobacterium, appeared to have a strong co-occurrence network in patients with CRC. 38 These microbial networks can be detected across ethnic and international boundaries.…”