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
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Can gut microbes cause pregnancy complications?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
MiBioGen included 18,340 participants from 24 cohorts and 211 bacterial taxa.
This study coordinated 16S rRNA gene sequencing profiles and genotyping data of 18,340 participants from 24 population-based cohorts comprising 211 bacterial taxa
FinnGen PPH GWAS had 3,670 cases and 98,626 controls.
PPH (3,670 cases and 98,626 controls)
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.
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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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