Publications
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Avershina, Ekaterina; Birkeland, Einar Elvbakken; Johannessen, Cecilie Bucher - & Rounge, Trine Ballestad
(2026).
CRISPR-Cas immune repertoires as an ecological record of bacterial interactions with mobile genetic elements in the human gut.
Gut microbes.
ISSN 1949-0976.
18(1).
doi:
10.1080/19490976.2026.2734649.
Full text in Research Archive
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Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Avershina, Ekaterina; Johannessen, Cecilie Bucher -; Bemanian, Vahid & Blix, Hege Salvesen
[Show all 14 contributors for this article]
(2026).
Microbiome signatures for detection of colorectal lesions in population-based FIT screening.
Nature Communications.
17.
doi:
10.1038/s41467-026-75962-1.
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The gut microbiome has been linked to colorectal cancer (CRC) development, with microbe-based classifiers distinguishing between CRC patients and healthy controls. However, there is a lack of studies addressing the utility of the microbiome in screening-relevant settings, including both precancers and CRC. In this Norwegian population-based study, we used fecal immunochemical test (FIT) leftovers from 1034 FIT-positive (i.e. positive for occult blood) screening participants for gut metagenome profiling using shotgun sequencing. Using comprehensive clinical, demographic, and lifestyle data, we modeled gut microbiome associations with CRC screening outcomes. Combining microbial profiles with quantitative FIT values improved detection of premalignant lesions beyond optimizing the FIT value alone, even after incorporating established CRC risk factors. Still, the FIT value maintained superior discriminative ability for CRC. We confirmed enrichment of bacteria such as Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC. In contrast, other bacteria previously associated with the presence of CRC, including Hungatella hathewayi and Clostridium symbiosum, as well as pks-negative Escherichia coli, were enriched in those with no neoplastic findings, suggesting that in a FIT-positive population their presence may reflect other conditions causing intestinal bleeding rather than underlying neoplasia. Microbial profiles were predominantly associated with distal rather than proximal lesions. Together, our findings highlight the potential for microbial markers to improve FIT-based CRC screening, especially by differentiating those with premalignant lesions from those who test FIT-positive for other reasons.
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Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Avershina, Ekaterina; Botteri, Edoardo; Bucher-Johannessen, Cecilie & Knudsen, Markus Dines
[Show all 14 contributors for this article]
(2026).
Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator.
European Journal of Nutrition.
ISSN 1436-6207.
65(4),
p. 1–18.
doi:
10.1007/s00394-026-03960-6.
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Background
Alcohol consumption is one of the major risk factors of colorectal cancer (CRC), yet the mechanisms underlying
this relationship, particularly the role of gut microbes, are not fully understood.
Objective To study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening
participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake
and colorectal lesions.
Methods Screening participants with a positive faecal immunochemical test at ages 55–77 were eligible for the CRCbiome
study. Alcohol intake was assessed using a validated, semi-quantitative food frequency questionnaire and linked with shotgun
metagenome based gut microbial profiles to study associations with screen-detected colorectal lesions. The potential
role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was
examined using causal mediation analysis.
Results Of 1468 participants with dietary data, 414 were diagnosed with advanced lesions. Alcohol intake was positively
associated with advanced lesions in a dose-dependent manner (ptrend = 0.008), with odds ratio of 1.09 (95% confidence
interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by
a distinct microbial profile, manifested as modest, but consistent, shifts in α- and β-diversity, and differentially abundant
bacteria. A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was
mediated by alcohol-associated gut bacteria.
Conclusion Alcohol consumption was associated with a distinct microbial profile, which partly explained the association
between alcohol intake and advanced colorectal lesions.
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Bucher-Johannessen, Cecilie; Senthakumaran, Thulasika; Avershina, Ekaterina; Birkeland, Einar Elvbakken; Hoff, Geir Svein & Bemanian, Vahid
[Show all 8 contributors for this article]
(2024).
Species-level verification of Phascolarctobacterium association with colorectal cancer.
mSystems.
9(10).
doi:
10.1128/msystems.00734-24.
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We have previously demonstrated an association between increased abundance of Phascolarctobacterium and colorectal cancer (CRC) and adenomas in two independent Norwegian cohorts. Here we seek to verify our previous findings using new cohorts and methods. In addition, we characterize lifestyle and sex specificity, the functional potential of the Phascolarctobacterium species, and their interaction with other microbial species. We analyze Phascolarctobacterium with 16S rRNA sequencing, shotgun metagenome sequencing, and species-specific qPCR, using 2350 samples from three Norwegian cohorts-CRCAhus, NORCCAP, and CRCbiome-and a large publicly available data set, curatedMetagenomicData. Using metagenome-assembled genomes from the CRCbiome study, we explore the genomic characteristics and functional potential of the Phascolarctobacterium pangenome. Three species of Phascolarctobacterium associated with adenoma/CRC were consistently detected by qPCR and sequencing. Positive associations with adenomas/CRC were verifi
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Bucher-Johannessen, Cecilie; Birkeland, Einar Elvbakken; Vinberg, Elina; Bemanian, Vahid; Hoff, Geir Svein & Berstad, Paula
[Show all 7 contributors for this article]
(2023).
Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing.
Frontiers in Oncology.
13.
doi:
10.3389/fonc.2023.1183039.
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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: From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the 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 with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was 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.
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Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Bucher-Johannessen, Cecilie; Vinberg, Elina; Nordby, Jan Inge & Kangas, Harri
[Show all 27 contributors for this article]
(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.
21.
doi:
10.1186/s12885-021-08640-8.
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Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.
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Bucher-Johannessen, Cecilie; Page, Christian Magnus; Haugen, Trine B.; Wojewodzic, Marcin; Fosså, Sophie Dorothea & Grotmol, Tom
[Show all 8 contributors for this article]
(2019).
Cisplatin treatment of testicular cancer patients introduces long-term changes in the epigenome.
Clinical Epigenetics.
11:179,
p. 1–13.
doi:
10.1186/s13148-019-0764-4.
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<i>Background</i> - Cisplatin-based chemotherapy (CBCT) is part of standard treatment of several cancers. In testicular cancer (TC) survivors, an increased risk of developing metabolic syndrome (MetS) is observed. In this epigenome-wide association study, we investigated if CBCT relates to epigenetic changes (DNA methylation) and if epigenetic changes render individuals susceptible for developing MetS later in life. We analyzed methylation profiles, using the MethylationEPIC BeadChip, in samples collected ~ 16 years after treatment from 279 Norwegian TC survivors with known MetS status. Among the CBCT treated (<i>n</i> = 176) and non-treated (<i>n</i> = 103), 61 and 34 developed MetS, respectively. We used two linear regression models to identify if (i) CBCT results in epigenetic changes and (ii) epigenetic changes play a role in development of MetS. Then we investigated if these changes in (i) and (ii) links to genes, functional networks, and pathways related to MetS symptoms.<p> <p><i>Results</i> - We identified 35 sites that were differentially methylated when comparing CBCT treated and untreated TC survivors. The PTK6–RAS–MAPk pathway was significantly enriched with these sites and infers a gene network of 13 genes with <i>CACNA1D</i> (involved in insulin release) as a network hub. We found nominal MetS-associations and a functional gene network with <i>ABCG1</i> and <i>NCF2</i> as network hubs.<p> <p><i>Conclusion</i> - Our results suggest that CBCT has long-term effects on the epigenome. We could not directly link the CBCT effects to the risk of developing MetS. Nevertheless, since we identified differential methylation occurring in genes associated with conditions pertaining to MetS, we hypothesize that epigenomic changes may also play a role in the development of MetS in TC survivors. Further studies are needed to validate this hypothesis.
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Published
Aug. 6, 2026 2:52 PM
- Last modified
Aug. 6, 2026 2:52 PM
