Long term follow-up of colorectal cancer screening attendees identifies differences inPhascolarctobacterium spp. using 16S rRNA and metagenome sequencing

Abstract

Background: The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross sectional studies. However, there is a lack of studies using prospectively collected samples. Methods: We analysed 144 archived faecal samples from participants in the NORwegian Colorectal CAncer Prevention (NORCCAP) trial diagnosed with CRC or high-risk adenomas (HRA) at screening, or who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all samples, and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity, and differential abundance. Results: Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared to healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. were associated with time to CRC diagnosis. Conclusion: Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.

Species-level verification of Phascolarctobacterium association to colorectal cancer

“…Several studies have reported similar associations at the genus level 13, Peters, 201613, Peters, #1244 , with few having looked at species level. Both our previous work including 17 years of follow-up 5 , and Yachida et al 12 found increased abundance of P.…”

“…Succinyl-CoA is the intermediate compound of succinate in the TCA cycle and is released upon production of an ATP molecule 78 . In our previous work we showed a lower abundance of several pathways related to heme biosynthesis in high risk adenomas compared to healthy controls 5 .…”

“…16S rRNA sequencing data from CRCAhus and NORCCAP were processed using Quantitative Insights Into Microbial Ecology (QIIME2 29 , version 2021.2.0 and 2020.2.0, respectively) with the DADA2-plugin as described previously 5,6 , resulting in ASV. For comparative analysis with metagenomic data, ASV counts were transformed to relative abundances using the transform_sample_counts function from the Phyloseq package 30 (v1.26.1) where each ASV count was divided by the total count of ASVs in the sample.…”

“…We have previously shown an increased abundance of Amplicon Sequence Variants (ASV) belonging to the genus Phascolarctobacterium in CRC and adenoma cases when compared to healthy controls in stool samples and tissue samples in two independent Norwegian cohorts 5,6 . Three species of Phascolarctobacterium; Phascolarctobacterium succinatutens, Phascolarctobacterium faecium, and Phascolarctobacterium wakonense have been described…”

Exploring the gut virome in fecal immunochemical test stool samples reveals novel associations with lifestyle in a large population-based study

“…The gut virome has also been associated with diseases such as inflammatory bowel disease and type 2 diabetes 15,16 . Dysregulation of gut bacteria and abundance of certain bacteria [17][18][19] are also proposed features of the association between the gut microbiome and 3 colorectal cancer development 20 . These changes in the bacteriome are likely to be accompanied by phage dysregulation 21 .…”