Long-term follow-up of colorectal cancer screening attendees identifies differences in <i>Phascolarctobacterium</i> spp. using 16S rRNA and metagenome sequencingOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study asked whether the gut microbiome differs years before colorectal cancer (CRC) is diagnosed. It used prospectively collected faecal samples from a Norwegian screening trial. Samples came from screening attendees later diagnosed with CRC or high-risk adenoma, and from people who stayed cancer-free over 17 years of follow-up. All samples underwent 16S rRNA sequencing, and a subset had shotgun metagenome sequencing. The team compared diversity, composition, and differential abundance of taxa and pathways.
Who was studied?
The study analyzed 144 archived faecal samples from participants in the Norwegian Colorectal Cancer Prevention (NORCCAP) trial. Samples were collected at screening and stored for up to 17 years. Groups included participants diagnosed with CRC, participants with high-risk adenoma (HRA), and controls who remained cancer-free during follow-up. All 144 samples had 16S sequencing, and 47 samples had metagenome sequencing. One individual was excluded because of an Escherichia coli infection.
What were the most important findings?
Overall diversity and composition did not differ significantly between CRC, HRA, and controls. However, specific taxa were differentially abundant in both datasets. The succinate-consuming genus Phascolarctobacterium, and Phascolarctobacterium succinatutens specifically, was significantly more abundant in CRC than controls in both 16S and metagenome data. This genus converts succinate to propionate and is linked to inflammation. Bifidobacterium and four Lachnospiraceae members were associated with time to CRC diagnosis. Several heme and TCA-cycle pathways were lower in high-risk adenoma.
What are the greatest implications of this study?
This is described as the first study of gut samples collected years before CRC diagnosis. It shows CRC-associated taxa are detectable long before clinical cancer appears. Phascolarctobacterium and taxa tied to time-to-diagnosis are proposed as candidates for further study as early markers. Detection before symptoms could support fecal-based screening. The study lacked data on diet, lifestyle, BMI, and antibiotics, so confounding may have created false-positive associations. Samples stored 17 years may also be partly degraded. Larger controlled studies are needed.