Women and men exhibit distinct gut microbial profiles linked to colorectal cancer development
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Background
The gut microbiome has emerged as a promising source of biomarkers to enhance early detection of colorectal cancer (CRC). However, sex-specific differences in gut microbial profiles and their relationship to CRC risk remain underexplored.
Objective
To investigate sex differences in screening-detected colorectal lesions and gut microbial profiles, as well as the potential for sex-specific associations between the gut microbiome and colorectal lesions.
Methods
This cross-sectional study included 1,034 faecal immunochemical test-positive screening participants aged 55–77 years recruited from the Norwegian CRCbiome study. Shotgun metagenomic sequencing was used to generate taxonomic and functional profiles of the gut microbiome, which were integrated with clinicopathological, demographic, and lifestyle data. Associations between sex, colorectal lesions, and microbial characteristics – including α-diversity, β-diversity, and abundances of bacterial species and functions – were assessed, including their interactions.
Results
Male participants had significantly higher odds of presenting with both non-advanced (OR: 1.50; 95% CI: 1.00–2.26) and advanced (OR: 1.46; 95% CI: 1.10–1.93) colorectal lesions compared to women. Gut microbial profiles differed markedly by sex, demonstrating compositional shifts and distinct bacterial profiles (19 taxa and 58 functions more abundant in men, 13 bacteria and 41 functions more abundant in women). In women, microbial α-and β-diversity varied across lesion subtypes, whereas no such differences were observed in men. Interaction analyses identified 5 bacteria and 6 functions that were differentially associated with colorectal lesions by sex.
Conclusion
This study highlights sex-specific differences in the gut microbiome and their association with colorectal lesions, emphasising the need to take sex into account in future research aiming to enhance CRC prevention strategies and treatment.
