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).
- Profiling small RNAs in fecal immunochemical tests: is it possible? Mol Cancer. doi: 10.1186/s12943-023-01869-w
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).
- Evaluating gut microbiota profiles from archived fecal samples, BMC Gastroenterology. doi:10.1186/s12876-018-0896-6
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.