Can gut microbes cause pregnancy complications?
Two-sample MR of 18,340 MiBioGen participants versus FinnGen pregnancy GWAS found taxon-specific IVW signals—e.g. Deltaproteobacteria raising PPH risk (OR 1.26) and Butyricimonas lowering it (OR 0.79).
Source
Causal associations between gut microbiota and adverse pregnancy outcomes: A two-sample Mendelian randomization study
Study at a glance
- Design
- Mendelian randomisation — Two-sample MR of MiBioGen gut-microbiome GWAS vs FinnGen R5 adverse pregnancy outcomes, IVW primary with MR-Egger/MR-PRESSO
- N
- N=18340 · MiBioGen exposure GWAS: 18,340 participants, 24 cohorts, 196 taxa after dropping unnamed taxa; FinnGen R5 outcomes include PPH 3,670/98,626 and GDM 5,687/117,892
- Population
- Host-genetics–microbiome GWAS (MiBioGen) and Finnish pregnancy-complication GWAS (FinnGen R5)
- Outcome
- IVW odds ratios for postpartum hemorrhage, abruptio placentae, spontaneous abortion, PROM, GDM, preeclampsia/eclampsia, and preterm birth
Structured fields used in claim comparison tables when every cited study has a complete layer.
What they did
Used locus-wide SNPs (p < 1×10⁻⁵) from MiBioGen 16S/genotype data (18,340 people; 196 taxa) as instruments for six FinnGen R5 adverse pregnancy outcomes, with IVW as the main estimator plus MR-Egger, MR-PRESSO, Cochran Q, and leave-one-out.
What they found
Several genera showed IVW associations: Deltaproteobacteria with higher PPH (OR 1.26, 1.00–1.59), Butyricimonas with lower PPH (OR 0.79), and mixed AP/GDM signals including Holdemanella OR 0.41 for abruptio placentae. All F statistics were >10.
The limits
What it doesn't show
MR of 16S taxa is not a trial of probiotics; FinnGen endpoints are coded diagnoses, SNPs were not genome-wide significant (p < 1×10⁻⁵), and horizontal pleiotropy can remain even after MR-PRESSO.
Key terms
- Two-sample MR
- Causal estimate using genetic instruments for exposure from one GWAS and outcomes from another.
- IVW
- Inverse-variance weighted combination of SNP-specific Wald ratios; primary estimator here.
- MiBioGen
- Multi-ethnic host-genetics–gut microbiome GWAS (18,340 people; 24 cohorts).
- FinnGen R5
- Finnish biobank GWAS used for pregnancy-complication outcomes.
- Instrumental variable
- SNP assumed to affect the outcome only through the exposure taxon.
- APOs
- Adverse pregnancy outcomes such as PPH, GDM, PROM, and preeclampsia.
Flashcards
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Common questions
What was the exposure GWAS?
MiBioGen: 18,340 participants from 24 cohorts and 196 named taxa.
What was the main MR method?
Inverse-variance weighted (IVW) estimates.
Were instruments weak?
No—F statistics were all larger than 10.
Did Deltaproteobacteria raise PPH risk?
IVW OR 1.26 (1.00–1.59), p = 0.047.
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