Publikasjoner
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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.
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Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Avershina, Ekaterina; Johannessen, Cecilie Bucher -; Bemanian, Vahid & Blix, Hege Salvesen
[Vis alle 14 forfattere av denne artikkelen]
(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
[Vis alle 14 forfattere av denne artikkelen]
(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),
s. 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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Glenna, Susanne; Birkeland, Einar Elvbakken; Orr, Russell; Gilfillan, Gregor; Dalland, Marianne & Økstad, Ole Andreas
[Vis alle 8 forfattere av denne artikkelen]
(2025).
Skin bacterial community dynamics of hands and forearms before and after military field exercise.
Microbiology spectrum.
13(5).
doi:
10.1128/spectrum.02953-24.
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The human skin microbiome is crucial for health and immunity, especially under the extreme conditions military personnel face. Soldiers often encounter unique stressors and hygienic challenges that can alter their skin’s microbial composition, particularly in field environments. In this study, we aimed to investigate the impact of military field exercises on the diversity and composition of the skin bacterial microbiota using 16S rRNA sequencing. We conducted a longitudinal study of Norwegian soldiers (n = 19) participating in outdoor training operations during the NATO winter exercise Cold Response 2022. Skin swabs were taken from soldiers' hands and forearms before and after the 10-day military exercise, and following a 3-week post-exercise leave. Our results reveal hand- and forearm-specific shifts in bacterial populations associated with the exercise, likely influenced by environmental exposure, reduced hygiene, and heightened social contact. Alpha diversity increased on forearms while remaining stable on hands, which appeared more resilient to perturbations. Both sites exhibited temporal changes in composition, with soil- and water-associated bacteria enriched post-exercise; most being transient on hands but more sustained on forearms. The soldiers’ microbiomes converged during the exercise, then diverged in the post-exercise leave period, and neither skin site returned to baseline composition at follow-up. Our findings highlight the impact of collaborative outdoor activities on microbial communities and suggest that resilience and stability differ between skin sites.
IMPORTANCE Optimizing soldier health and resilience is critical for maintaining military readiness and operational effectiveness. The skin, as the body’s first line of defense, is subjected to numerous challenges in military environments. Unique environmental and hygiene challenges can disrupt the skin microbiome and increase susceptibility to skin and soft tissue infections. This longitudinal research provides valuable insights into the effects of military service on the bacterial dynamics of the skin microbiome but can also inform hygiene management and disease prevention in comparable situations.
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Bucher-Johannessen, Cecilie; Senthakumaran, Thulasika; Avershina, Ekaterina; Birkeland, Einar Elvbakken; Hoff, Geir Svein & Bemanian, Vahid
[Vis alle 8 forfattere av denne artikkelen]
(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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Istvan, Paula; Birkeland, Einar Elvbakken; Avershina, Ekaterina; Kværner, Ane Sørlie; Bemanian, Vahid & Pardini, Barbara
[Vis alle 11 forfattere av denne artikkelen]
(2024).
Exploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study.
Nature Communications.
15.
doi:
10.1038/s41467-024-46033-0.
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Abstract Stool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identify, annotate and characterize more than 18000 DNA viruses, using shotgun metagenome sequencing. Only six percent of them are assigned to a known taxonomic family, with Microviridae being the most prevalent viral family. Linking individual profiles to comprehensive lifestyle and demographic data shows 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibit strong and consistent associations with both diversity and relative abundance of individual viruses, as well as with enrichment for auxiliary metabolic genes. We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.
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Bucher-Johannessen, Cecilie; Birkeland, Einar Elvbakken; Vinberg, Elina; Bemanian, Vahid; Hoff, Geir Svein & Berstad, Paula
[Vis alle 7 forfattere av denne artikkelen]
(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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Birkeland, Einar Elvbakken; Ferrero, Giulio; Pardini, Barbara; Umu, Sinan Ugur; Tarallo, Sonia & Bulfamante, Sara
[Vis alle 10 forfattere av denne artikkelen]
(2023).
Profiling small RNAs in fecal immunochemical tests: is it possible?
Molecular Cancer.
22:161(1),
s. 1–7.
doi:
10.1186/s12943-023-01869-w.
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Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.
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Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Vinberg, Elina; Hoff, Geir; Hjartåker, Anette & Rounge, Trine Ballestad
[Vis alle 7 forfattere av denne artikkelen]
(2022).
Associations of red and processed meat intake with screen-detected colorectal lesions.
British Journal of Nutrition.
ISSN 0007-1145.
s. 1–36.
doi:
10.1017/S0007114522002860.
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Limited data exist regarding the role of meat consumption in early-stage colorectal carcinogenesis. We examined associations of red and processed meat intake with screen-detected colorectal lesions in immunochemical fecal occult blood test (FIT)-positive participants, enrolled in the Norwegian CRCbiome study during 2017-2021, aged 55-77 years. Absolute and energy-adjusted intakes of red and processed meat (combined and individually) were assessed using a validated, semiquantitative food frequency questionnaire. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1,162 participants with available dietary data, 319 (27%) presented with advanced colorectal lesions at colonoscopy. High vs low energy-adjusted intakes of red and processed meat combined, as well as red meat alone, were borderline to significantly positively associated with advanced colorectal lesions (ORs (95% CIs) of 1.24 (0.98, 1.57) and 1.34 (1.07, 1.69), respectively). A significant dose-response-relationship was also observed for absolute intake levels (OR (95% CI) of 1.32 (1.09, 1.60) per 100 g/day increase in red and processed meat). For processed meat, no association was observed between energy-adjusted intakes and advanced colorectal lesions. A significant positive association was, however, observed for the small proportion of participants (10%) with absolute intake levels ≥100 vs <50 g/day (OR (95% CI) of 1.19 (1.09, 1.31)). In summary, high intakes of red and processed meat were associated with presence of advanced colorectal lesions at colonoscopy in FIT-positive participants. The study demonstrates a potential role of using dietary data to improve the performance of FIT-based screening.
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Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Bucher-Johannessen, Cecilie; Vinberg, Elina; Nordby, Jan Inge & Kangas, Harri
[Vis alle 27 forfattere av denne artikkelen]
(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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Aakko, Sofia; Straume, Anne Hege; Birkeland, Einar Elvbakken; Chen, Ping; Qiao, Xi & Lønning, Per Eystein
[Vis alle 7 forfattere av denne artikkelen]
(2019).
MYC-induced miR-203b-3p and miR-203a-3p control Bcl-xL expression and paclitaxel sensitivity in tumor cells.
Translational Oncology.
ISSN 1944-7124.
12(1),
s. 170–179.
doi:
10.1016/j.tranon.2018.10.001.
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Taxanes are chemotherapeutic agents used in the treatment of solid tumors, particularly of breast, ovarian, and lung origin. However, patients show divergent therapy responses, and the molecular determinants of taxane sensitivity have remained elusive. Especially the signaling pathways that promote death of the taxane-treated cells are poorly characterized. Here we describe a novel part of a signaling route in which c-Myc enhances paclitaxel sensitivity through upregulation of miR-203b-3p and miR-203a-3p; two clustered antiapoptosis protein Bcl-xL controlling microRNAs. In vitro, the miR-203b-3p decreases the expression of Bcl-xL by direct targeting of the gene's mRNA 3’UTR. Notably, overexpression of the miR-203b-3p changed the fate of paclitaxel-treated breast and ovarian cancer cells from mitotic slippage to cell death. In breast tumors, high expression of the miR-203b-3p and MYC was associated with better therapy response and patient survival. Interestingly, in the breast tumors, MYC expression correlated negatively with BCL2L1 expression but positively with miR-203b-3p and miR-203a-3p. Finally, silencing of MYC suppressed the transcription of both miRNAs in breast tumor cells. Pending further validation, these results may assist in patient stratification for taxane therapy.
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Birkeland, Einar Elvbakken; Zhang, Shan; Poduval, Deepak; Geisler, Jürgen; Nakken, Sigve & Vodak, Daniel
[Vis alle 11 forfattere av denne artikkelen]
(2018).
Patterns of genomic evolution in advanced melanoma.
Nature Communications.
9:2665,
s. 1–12.
doi:
10.1038/s41467-018-05063-1.
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Genomic alterations occurring during melanoma progression and the resulting genomic heterogeneity between metastatic deposits remain incompletely understood. Analyzing 86 metastatic melanoma deposits from 53 patients with whole-exome sequencing (WES), we show a low branch to trunk mutation ratio and little intermetastatic heterogeneity, with driver mutations almost completely shared between lesions. Branch mutations consistent with UV damage indicate that metastases may arise from different subclones in the primary tumor. Selective gain of mutated BRAF alleles occurs as an early event, contrasting whole-genome duplication (WGD) occurring as a late truncal event in about 40% of cases. One patient revealed elevated mutational diversity, probably related to previous chemotherapy and DNA repair defects. In another patient having received radiotherapy toward a lymph node metastasis, we detected a radiotherapy-related mutational signature in two subsequent distant relapses, consistent with secondary metastatic seeding. Our findings add to the understanding of genomic evolution in metastatic melanomas.
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Gansmo, Liv Beathe; Bjørnslett, Merete Pauline; Halle, Mari Kyllesø; Salvesen, Helga; Dørum, Anne & Birkeland, Einar Elvbakken
[Vis alle 11 forfattere av denne artikkelen]
(2016).
The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer.
Tumour Biology.
ISSN 1010-4283.
37(8),
s. 10697–10702.
doi:
10.1007/s13277-016-4940-2.
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The MDM4 protein (also known as MDMX or HDMX) is a negative regulator of p53, not only by direct interaction but also through its interaction with MDM2. Further, MDM4 overexpression and amplification have been observed in several cancer forms. Recently, a single nucleotide polymorphism (SNP) in the 3’ untranslated region of the MDM4 gene, SNP34091A > C (rs4245739) was reported to alter MDM4 messenger RNA (mRNA) stability by modulating a microRNA binding site, thereby leading to decreased MDM4 levels. In this case-control study, we aimed to evaluate the possible association between MDM4 SNP34091 status and cancer risk by comparing the genotype frequencies in large hospital-based cohorts of endometrial- (n = 1404) and ovarian (n = 1385) cancer patients with healthy female controls (n = 1870). Genotype frequencies were compared by odds ratio (OR) estimates and Fisher exact tests. We found that individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer (SOC) in general and high-grade serous ovarian cancer (HGSOC) in particular (SOC: OR = 1.18., 95 % CI = 1.01–1.39; HGSOC: OR = 1.25, CI = 1.02–1.53). No association between SNP34091 genotypes and endometrial cancer risk was observed. Our data indicate the MDM4 SNP34091AC/CC genotypes to be associated with an elevated risk for SOC and in particular the HGSOC type.
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Gansmo, Liv Beathe; Romundstad, Pål Richard; Birkeland, Einar Elvbakken; Hveem, Kristian; Vatten, Lars Johan & Knappskog, Stian
[Vis alle 7 forfattere av denne artikkelen]
(2015).
MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk.
Cancer Medicine.
4(12),
s. 1901–1907.
doi:
10.1002/cam4.555.
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The MDM4 protein plays an important part in the negative regulation of the tumor suppressor p53 through its interaction with MDM2. In line with this, MDM4 amplification has been observed in several tumor forms. A polymorphism (rs4245739 A>C; SNP34091) in the MDM4 3′ untranslated region has been reported to create a target site for hsa-miR- 191, resulting in decreased MDM4 mRNA levels. In this population-based case–control study, we examined the potential association between MDM4 SNP34091, alone and in combination with the MDM2 SNP309T>G (rs2279744), and the risk of breast-, colon-, lung-, and prostate cancer in Norway. SNP34091 was genotyped in 7,079 cancer patients as well as in 3,747 gender-and age-matched healthy controls. MDM4 SNP34091C was not associated with risk for any of the tumor forms examined, except for a marginally significant association with reduced risk for breast cancer in a recessive model (OR = 0.77: 95% CI = 0.59–0.99). Stratifying according to MDM2 SNP309 status, we observed a reduced risk for breast cancer related to MDM4 SNP34091CC among individuals harboring the MDM2 SNP309GG genotype (OR = 0.41; 95% CI = 0.21–0.82). We conclude, MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung-, colon-or prostate cancer.
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Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Istvan, Paula; Bermanian, Vahid; Bucher-Johannessen, Cecilie & Avershina, Ekaterina
[Vis alle 9 forfattere av denne artikkelen]
(2022).
The microbiome in fecal immunochemical tests from colorectal cancer screening participants – can it be used as a screening biomarker?
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Avershina, Ekaterina; Birkeland, Einar Elvbakken; Berstad, Paula; Hoff, Geir Svein & Rounge, Trine Ballestad
(2022).
Total neoplastic polyp volume is correlated to several bacterial taxa in faecal immunochemical test-positive CRC-screening participants.
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Avershina, Ekaterina; Birkeland, Einar Elvbakken; Berstad, Paula; Hoff, Geir Svein & Rounge, Trine Ballestad
(2022).
Total neoplastic polyp volume is correlated to several bacterial taxa in faecal immunochemical test-positive CRC-screening participants.
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Istvan, Paula; Birkeland, Einar Elvbakken; Rognes, Torbjørn & Rounge, Trine Ballestad
(2021).
Profiling gut viruses from metagenomes of Bowel Cancer Screening participants.
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Publisert
7. des. 2022 09:18
- Sist endret
10. sep. 2025 07:18