Same Stool Test, Different Microbiome Clues? What a Norwegian Screening Study Found
Colon cancer screening looks beautifully simple from the outside. You mail in a stool sample, a machine looks for hidden blood, and if the test is positive you get a colonoscopy.
But screening performance and colorectal cancer risk are not identical in women and men. Previous research has reported sex differences in colorectal cancer incidence and in the performance of blood-based stool screening tests. The new study did not directly test whether FIT itself works differently by sex. Instead, it asked whether the microbial clues present in FIT-positive stool samples differ between women and men.
So a Norwegian team asked a more specific question: among people already referred to colonoscopy after a positive FIT, do the gut microbiome patterns associated with colorectal lesions look the same in women and men?
What the study found
1. A large screening-relevant dataset. All 1,034 participants (452 women, 582 men, aged 55–77) had a positive FIT and then underwent colonoscopy, allowing microbiome findings to be compared with actual colonoscopy outcomes. Residual stool from the FIT kits was analysed with shotgun metagenomic sequencing, which can provide species-level taxonomic profiles and infer microbial gene and pathway content. It measures functional potential, not what the microbes were actively doing in the gut at that moment.
2. Men had higher odds of colorectal lesions, and measured lifestyle factors did not fully account for it. Compared with women, men had higher odds of non-advanced lesions (OR 1.50, 95% CI 1.00–2.26) and advanced lesions (OR 1.46, 95% CI 1.10–1.93). Adjustment for measured lifestyle and demographic factors only modestly changed the estimates. That does not prove a biological cause; residual confounding can remain in an observational study.
3. Women and men had measurably different gut microbial profiles. After adjustment for lifestyle and demographic factors, 32 bacterial taxa and 99 functional features differed between the sexes. Paraprevotella clara and Bifidobacterium adolescentis showed the strongest associations with male sex, while Eggerthella lenta and Streptococcus thermophilus were most strongly associated with female sex. Overall community composition also differed statistically by sex, although the effect size was small. The study did not establish why these sex differences exist.
4. The lesion-associated microbiome signal looked stronger in women — but the statistics need care. In women, both α-diversity and β-diversity differed across colonoscopy groups, whereas no significant diversity differences across colonoscopy groups were detected in men. However, the formal sex-by-lesion interaction tests for these diversity measures were not statistically significant. In exploratory differential-abundance analyses, more taxa and functional features were flagged in women than in men, and five bacterial taxa and nine functional features showed formal sex-specific interaction signals.
5. pks-positive E. coli produced an intriguing women-only signal — but not a confirmed sex difference. Some E. coli strains carry the pks gene cluster, which encodes the genotoxin colibactin and has been linked in other research to characteristic DNA damage in colorectal carcinogenesis. In this study, pks-positive E. coli was significantly associated with colorectal cancer in women but not in men. Crucially, the formal interaction between sex and pks status was not significant, so “significant in women only” should not be read as proof that the association truly differs by sex.
6. Most previously reported CRC-associated bacteria did not show convincing sex specificity. Known colorectal cancer-associated taxa, including Fusobacterium nucleatum, showed broadly similar effect patterns in women and men. This argues against assuming that every established microbial marker needs a different interpretation by sex, even though some community-level and specific taxonomic associations may differ.
Now the part the headline can't fit
This is a snapshot, not a film. Stool was collected once, at one moment in the disease process. The study cannot say whether bacteria helped cause the lesions, or simply moved in after them — or whether a bleeding polyp itself reshapes the local bacterial neighbourhood.
The “women-only” findings were not statistically confirmed as sex differences. This is the subtlest and most important caveat. Women showed a signal and men did not — but when the authors formally tested whether the difference between sexes was real, the interaction tests were not significant (P = 0.066 for one diversity measure). “Significant in one group, not in the other” is not the same as “significantly different between groups.” The same applies to the pks E. coli result, where the number of cancer cases was small and the authors explicitly urge caution.
Everyone here had already tested FIT-positive. The “no neoplasia” comparison group was therefore not a random sample of healthy adults; these participants had occult blood detected but no colorectal neoplasia found at colonoscopy. Other causes of FIT positivity may influence the microbiome, which limits how directly these findings can be transferred to FIT-negative populations or general screening populations.
The participants were a relatively narrow population. They were Norwegian screening participants aged 55–77 years, all FIT-positive. Diet, medication use, geography and other host factors can shape the microbiome, so the exact microbial signatures need external validation in more diverse screening populations.
This is biomarker discovery, not a ready-to-use clinical test. Shotgun metagenomic sequencing remains substantially more complex than routine FIT. The practical goal is to identify microbial features that might eventually be converted into targeted, validated assays or combined with quantitative FIT — not to replace today's screening with whole-metagenome sequencing tomorrow.
Here's how I'd read this as a doctor.
Nothing here changes current screening recommendations. This study did not test a new clinical screening strategy and does not justify different FIT thresholds or screening intervals for women and men. If a screening programme recommends follow-up colonoscopy after a positive FIT, these microbiome findings are not a reason to skip or delay it.
Don't treat a commercial microbiome panel as a colorectal cancer screening test. This paper is a discovery study, not validation of a consumer diagnostic. Any future microbiome-based classifier will need external validation and should be checked for performance in women and men rather than assuming one model works equally well for everyone.
The useful lesson is methodological. The study shows that sex can modify some microbiome–lesion associations and that pooled analyses may hide patterns visible within subgroups. Future microbiome-based CRC biomarkers should therefore report and validate performance by sex. Whether doing so actually improves screening accuracy or reduces false positives still has to be tested prospectively.
This post is a plain-language summary of published research and is not medical advice. The study described is cross-sectional and cannot show cause and effect. Follow your national screening recommendations and discuss any bowel symptoms — especially bleeding, persistent changes in bowel habit, or unexplained weight loss — with your doctor.
Source
Bucher-Johannessen C, Kvaerner AS, Birkeland E, et al. Gut microbiome signatures of colorectal cancer development are more pronounced in women compared to men in a population-based screening cohort. Biology of Sex Differences. Published 17 September 2026. doi:10.1186/s13293-026-00985-8
Trial registration: Bowel Cancer Screening in Norway (BCSN), ClinicalTrials.gov NCT01538550
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