Mendelian randomisation associates specific gut taxa with several cancers
Genetic instruments for gut microbiota taxa showed causal associations with breast, lung, colorectal, prostate, gastric, and head/neck cancers—sometimes in opposing directions for the same genus.
Source
Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study
Study at a glance
- Design
- Mendelian randomisation — Two-sample MR of MiBioGen gut taxa instruments against eight cancer GWAS summary sets
- N
- 211 taxa instruments; cancer GWAS sample sizes vary by malignancy — no single primary N
- Population
- Gut microbiome and cancer GWAS summary statistics (IEU OpenGWAS/consortia)
- Outcome
- Causal microbiome–cancer associations (stringent and sensitivity analyses)
Structured fields used in claim comparison tables when every cited study has a complete layer.
What they did
Authors harmonized MiBioGen gut microbiome GWAS instruments (211 taxa) with cancer GWAS summary statistics for eight malignancies from IEU Open GWAS and consortia. They ran two-sample MR (IVW, MR-Egger, weighted median, MR-PRESSO) with Bonferroni thresholds, sensitivity analyses, and reverse MR to test directionality.
What they found
Eleven stringent microbiome-to-cancer causal relationships emerged, including Actinobacteria/Bifidobacteriales with higher breast cancer odds, Tyzzerella3 with higher lung adenocarcinoma but lower colorectal cancer risk, Ruminococcustorques group with lower prostate cancer risk, and Peptostreptococcaceae with higher gastric cancer risk. Reverse MR supported bidirectional Tyzzerella3–lung adenocarcinoma effects. Additional associations appeared at relaxed thresholds across datasets.
The limits
What it doesn't show
MR assumes valid genetic instruments and European-ancestry GWAS limits generalizability; 16S-based taxa lack strain resolution, and mechanistic pathways from taxa to cancer remain unproven experimentally.
Key terms
- Mendelian randomisation (MR)
- Uses genetic variants as instrumental variables to infer causal effects of exposures on outcomes.
- Two-sample MR
- Combines SNP-exposure and SNP-outcome associations from separate GWAS datasets.
- MiBioGen
- Consortium GWAS of human genetic variants associated with gut microbiota composition.
- Inverse-variance weighted (IVW)
- Primary MR estimator aggregating Wald ratios across SNPs, assuming balanced pleiotropy.
- MR-PRESSO
- Method detecting and removing outlier SNPs with horizontal pleiotropy in MR analyses.
- Instrumental variable (IV)
- Genetic SNP strongly associated with microbiota taxon abundance used to proxy exposure.
Flashcards
Research intelligence for this paper
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Quiz yourself
How many taxa were included from MiBioGen?
Common questions
Does this prove gut bacteria cause cancer directly?
MR supports causal genetic liability links, but experimental and clinical studies are still needed to confirm mechanisms and modifiability.
Why are Bifidobacteria linked to higher breast cancer here?
MR found Actinobacteria/Bifidobacteriales associated with increased breast cancer odds—contrasting with some probiotic narratives and highlighting taxon-specific effects.
Can the same genus affect cancers differently?
Yes—Tyzzerella3 associated with higher lung adenocarcinoma but lower colorectal cancer risk in MR analyses.
Was reverse causation tested?
Reverse MR showed lung adenocarcinoma also associated with Tyzzerella3, indicating bidirectional relationships for that pair.
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