CRCbiome publications

Einar E. Birkeland, Ane S. Kværner, Ekaterina Avershina, Cecilie Bucher-Johannessen, Vahid Bemanian, Hege S. Blix, Anette Hjartåker, Willem M. de Vos, Giske Ursin, Geir Hoff, Kristin R. Randel, Edoardo Botteri, Paula Berstad & Trine B. Rounge (2026)

In this study, we characterized the microbiome of the screening participants in CRCbiome, and compared the microbes present in those who had colorectal cancer (CRC) or its precursor to those who did not. Controlling for lifestyle, demographic, and clinical factors, we observed broad differences in diversity, composition, and community states, which were more pronounced for those with left-sided lesions. Using machine learning for prediction of colonoscopy findings, combining microbial signals with the FIT test used in screening, accuracy was improved for precancers, but not cancers. Evaluation of individual microbes reproduced previously reported associations for bacteria such as an enrichment of Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC, and indicated that several microbes previously suspected to be associated with disease were more common in those without CRC or precursors. Read "Behind the Paper" here.

Ane Sørlie Kværner, Einar Birkeland, Ekaterina Avershina, Edoardo Botteri, Cecilie Bucher-Johannessen, Markus Dines Knudsen, Anette Hjartåker, Christian M. Page, Johannes R. Hov, Mingyang Song, Kristin Ranheim Randel, Geir Hoff, Trine B. Rounge & Paula Berstad (2026)

  • Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator. European Journal of Nutrition. doi: 10.1007/s00394-026-03960-6

We integrated alcohol intake shotgun metagenome-based taxonomic and functional profiles of >1000 CRC screening participants aged 55-77 years. We observed a dose-response relationship, with a 10 g/day increase in alcohol intake increasing the risk for advanced lesions by 9 %. Alcohol consumers exhibited a distinct microbial profile compared to non-consumers and approximately 12% of the association between alcohol intake and advanced lesions could be explained by the microbiome.

Monica Linnea Dahlgren, Paula Berstad, Hege Berg Henriksen, Rune Blomhoff, and Ane Sørlie Kværner (2025)

  • Characterization of Nova-classified foods in a large cohort of Norwegian colorectal cancer screening participants. Norsk tidsskrift for ernæring. doi: https://doi.org/10.18261/ntfe.23.1.3

We used the dietary assessment in the CRCbiome participants to provide a detailed characterization of food intake classified according to processing level relevant to the Norwegian context, ranging from Nova category 1 (non-processed) to 4 (ultra-processed). Using the Nova classification on food-frequency data, a wide array of foods and beverages were classified as ultra-processed. Nova-classified ultra-processed food accounted for 50% of the energy intake (E%) of the study population (51 E% in men, 47 E% in women). Among ultra-processed foods, bread was the largest contributor to energy intake, making up 19% of total energy (20 E% in men, 18 E% in women).

Ekaterina Avershina, Arfa Irej Qureshi, Hanne C. Winther-Larsen & Trine B. Rounge (2025)

When exploring options for a reliable method for characterizing gut fungi, we observed the scarcity of both reference genomes for fungal species and of robust analytical tools. In fact, only approximately 10% of the fungal species we targeted, had a reference genome available in the NCBI RefSeq database and two fungi-specific tools operated smoothly without necessitating code modifications. When tested with simulated mock communities, the tools exhibited high incidence of false predictions, primarily resulting from inadequate databases’ quality. 

Cecilie Bucher-Johannessen, Thulasika Senthakumaran, Ekaterina Avershina, Einar Birkeland, Geir Hoff, Vahid Bemanian, Hege Tunsjø, Trine B Rounge (2024)

This study builds on our previous research that identified a link between the gut bacterium Phascolarctobacterium and colorectal cancer (CRC) in Norwegian cohorts. We aimed to validate these findings with new cohorts and advanced methods. By analyzing 2,350 samples from three Norwegian cohorts - CRCAhus, NORCCAP, and CRCbiome - as well as data from the curatedMetagenomicData, we explored the lifestyle and sex-specific factors, functional potential, and interactions of Phascolarctobacterium species with other microbes. Our results confirmed that P. succinatutens is more abundant in patients with adenomas/CRC, while P. faecium is less prevalent in adenoma cases. Notably, P. succinatutens was more common in men. Each species formed distinct microbial communities, suggesting different roles in CRC development. This study underscores the importance of recognizing P. succinatutens as a key bacterium associated with CRC.

Paula Istvan, Einar Birkeland, Ekaterina Avershina, Ane Soerlie Kvaerner, Vahid Bemanian, Barbara Pardini, Sonia Tarallo, Willem M. de Vos, Torbjoern Rognes, Paula Berstad & Trine B Rounge (2024).

  • Exploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study. Nature Communications. doi: https://doi.org/10.1038/s41467-024-46033-0

In recent years, our understanding of the microbiome, the communities of microorganisms inhabiting our bodies, particularly in the gut, has evolved significantly, revealing their crucial role in health and disease. Gut microbes, including bacteria and viruses, influence various aspects of our well-being, extending beyond gastrointestinal issues to immunological disorders and even colorectal cancer (CRC). Despite rising CRC rates globally, early detection methods like the fecal immunochemical test (FIT) often miss pre-cancerous lesions. The CRCbiome project, led by Prof. Rounge, aims to enhance FIT's efficacy by incorporating gut microbiome data from the test samples. Our research, utilizing over 1000 FIT samples, demonstrates the feasibility of analyzing the gut virome through these tests. Here we have uncovered diverse viral communities, strongly linked to lifestyle factors like smoking, exercise, and diet, suggesting the potential for personalized risk assessment and preventive measures against CRC development.

Einar Birkeland, Giulio Ferrero, Barbara Pardini, Sinan U. Umu, Sonia Tarallo, Sara Bulfamante, Geir Hoff, Carlo Senore, Trine B Rounge, Alessio Naccarati (2023).

In order to discover new non-invasive biomarkers for gastrointestinal diseases, there is a need for analysis of large biobanks. Regular population-wide sampling is commonly done in colorectal cancer screening programs with sampling optimized for detection of occult blood. In this study, we wanted to evaluate how these samples are suited for analysis of small RNAs. Small RNAs are produced by both humans and bacteria, acting as regulators of gene expression. Previous research has shown how these small RNAs are associated with risk of colorectal cancer. Here, we showed that small RNAs were robustly detected in samples collected as part of regular screening, at similar rates to those of standard methodology for fecal small RNA analysis. Even with limited power, we detected miRNA associations with the presence of colorectal cancer and its precursors, indicating the potential for biomarker discovery in small RNA analysis of colorectal cancer screening samples.

Ane Sørlie Kværner, Astrid Riseth Andersen, Hege Berg Henriksen, Markus Knudsen, Anne Marte Wetting Johansen, Anette Hjartåker, Siv Kjølsrud Bøhn, Ingvild Paur, Gro Wiedswang, Sigbjørn Smeland, Trine B. Rounge, Rune Blomhoff, Paula Berstad (2023).

  • Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) Cancer Prevention Recommendations with Stages of Colorectal Carcinogenesis. Cancer Medicine. doi: https://doi.org/10.1002/cam4.6119

Adherence to cancer prevention recommendations has been shown to lower risk of colorectal cancer. In this cross-sectional investigation among 1,486 CRCbiome participants, we document that adherence to cancer prevention recommendations also lower the probability of screen-detected advanced precancerous lesions. Although some recommendations seemed to be more important for risk reduction than others (i.e. limiting alcohol intake and having a normal body weight), we conclude that the best way of preventing precancerous lesions likely can be achieved by taking a holistic approach to cancer prevention.

C. Bucher-Johannessen, E. Birkeland, E. Vinberg, V. Bemanian, G. Hoff, P. Berstad, TB. Rounge (2023).

  • Long term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16s rRNA and metagenome sequencing. Frontiers in Oncology. doi: https://doi.org/10.3389/fonc.2023.1183039

This study aimed to investigate the potential association between the microbiome and colorectal cancer (CRC), using fecal samples collected prospectively. Using 16S rRNA and metagenome sequencing, 144 and 47 samples were analyzed respectively. We looked into differences in taxonomy and gene content between healthy controls, high risk adenomas and those that developed CRC during 17 years of follow-up. The study identified several taxa potentially associated with CRC, including Phascolarctobacterium succinatutens which was significant using both sequencing methods.

Ane Sørlie Kværner, Einar Birkeland, Elina Vinberg, Geir Hoff, Anette Hjartåker, Trine B Rounge, Paula Berstad (2022).

  • Associations of red and processed meat intake with screen-detected colorectal lesions. British Journal of Nutrition. doi: 10.1017/S0007114522002860

Red and processed meat are established risk factors of colorectal cancer. In this cross-sectional investigation among 1,162 FIT-positive participants of the CRCbiome, we examined whether those with a high meat consumption also had an increased risk of precancerous lesions. In line with what is observed for colorectal cancer, we observed that high intakes of red and processed meat (both absolute and energy adjusted intakes) were positively associated with screen-detected advanced colorectal lesions. Our results highlight the importance of early prevention strategies and suggest a potential for using dietary data to improve accuracy of FIT-based screening. 

Kværner AS, Birkeland E, Bucher-Johannessen C, Vinberg E, Nordby JI, Kangas H, Bemanian V, Ellonen P, Botteri E, Natvig E, Rognes T, Hovig E, Lyle R, Ambur OH, de Vos WM, Bultman S, Hjartåker A, Landberg R, Song M, Blix HS, Ursin G, Randel KR, de Lange T, Hoff G, Holme Ø, Berstad P, Rounge TB (2021).

  • The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants. BMC Cancer. doi: 10.1186/s12885-021-08640-8

This protocol paper describes the design and methodology of the CRCbiome study, aiming at developing a microbiome-based classification algorithm (likely in combination with FIT) for identification of advanced colorectal lesions at screening. The study is nested within the Bowel Cancer Screening in Norway (BSCN) trial, which is a pilot for the national screening program, currently being rolled out. With the use of metagenome sequencing and comprehensive questionnaire and registry data, we hope that the CRCbiome study will contribute to increased understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences early stage colorectal carcinogenesis. By evaluating biomarker performance in a screening setting, using samples from the target population, we believe that the generalizability of the findings to future screening cohorts should be high.

Rounge TB, Meisal R, Nordby JI, Ambur OH, de Lange T, Hoff G (2018).

This is a feasibility study showing that fecal samples collected as part of colorectal screening in Norway can be used for microbiota profiling. We could identify the same diversity of bacteria in Fecal Immunochemical Test (FIT) tubes as in fresh gut samples. While old samples from the NORCCAP study showed somewhat reduced diversity. We also showed that the analyses of blood in the FIT samples likely did not contaminate the FIT microbiome. This feasibility study was important in securing funding for the CRCbiome project. 

 

Published May 12, 2023 10:42 AM - Last modified Aug. 24, 2026 9:33 AM
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