Relationship between the microbiome and obesity-associated cancer risk using Mendelian randomisation
Authors' conclusion
Gut Actinobacteria may contribute to obesity-driven CRC risk, supporting the rationale of microbiome-targeted interventions to reduce CRC risk.
Study context
- Population
- Eight cancers (384,738 cases) of European ancestry
- Participants
- 384,738 cases
- Exposure
- Genetically predicted body mass index (BMI)/waist-to-hip ratio adjusted for BMI (WHRadjBMI), 211 gut microbial taxa and risk of eight cancers
- Outcome
- Causal links between genetically predicted BMI/WHRadjBMI, gut microbial taxa and cancer risk, and microbiome mediation
Methodological detailsmediation analysis, replication in FinnGen cohort
- Mediation analysis
- Replication in FinnGen cohort
Main finding
As reported in the abstract
Genetically predicted BMI and cancer risk
- CRC: OR per SD (95% CI); P
- 1.12 [1.06-1.17]; P = 4.95 × 10-6
- Kidney (RCC): OR per SD (95% CI); P
- 1.48 [1.34-1.63]; P = 1.61 × 10-15
- Endometrial: OR per SD (95% CI); P
- 1.70 [1.55-1.87]; P = 2.09 × 10-27
- Lung: OR per SD (95% CI); P
- 1.20 [1.12-1.29]; P = 1.40 × 10-7
- Oesophageal: OR per SD (95% CI); P
- 1.25 [1.13-1.39]; P = 3.09 × 10-5
Observational data: associations, not effects.
Further findings
Gut microbial taxa and CRC risk
- Microbial taxa associated with CRC risk
- 7
- Phylum Actinobacteria: OR per SD (95% CI); P
- 1.48 [1.29-1.70]; P = 1.78 × 10-8
- Class Actinobacteria: OR per SD (95% CI); P
- 1.36 [1.22-1.51]; P = 2.57 × 10-8
- Replicated in FinnGen
Mediation of BMI to CRC risk by Actinobacteria
- Phylum Actinobacteria: proportion mediated
- 29% [8-50] (95% CI)
- Class Actinobacteria: proportion mediated
- 21% [4-37] (95% CI)
- Collectively accounting for
- 50%
Microbiome mediation for other cancers
- No consistent microbiome mediation observed for other cancers
Original publication
Relationship between the microbiome and obesity-associated cancer risk using Mendelian randomisation. Int J Obes (Lond). Published 19 February 2026. doi:10.
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