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Published on: June 24, 2020
Causal associations between gut microbiota and premature rupture of membranes: a two-sample Mendelian randomization
Lei Zhang1,2, Qian Li1,2, Jiafeng Huang3
1Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing, China.
Background:
Previous study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate.
Methods:
A two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium's largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses.
Results:
The IVW method revealed that class Mollicutes (IVW, OR=0.773, 95%CI: 0.61-0.981, pval = 0.034), genus Marvinbryantia (IVW, OR=00.736, 95%CI: 0.555-0.977, pval = 0.034), genus Ruminooccaceae UCG003 (IVW, OR=0.734, 95%CI: 0.568-0.947, pval = 0.017) and phylum Tenericutes (IVW, OR=0.773, 95%CI: 0.566-1.067, pval = 0.034) were associated with a reduced risk of PROM, while genus Collinsella (IVW, OR=1.444, 95%CI: 1.028-2.026, pval = 0.034), genus Intestinibacter (IVW, OR=1.304, 95%CI: 1.047-1.623, pval = 0.018) and genus Turicibacter (IVW, OR=1.282, 95%CI: 1.02-1.611, pval = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (pval=0.045), genus Lachnoclostridium should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (pval >0.05).
Conclusions:
In this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.
Insights
This study used Mendelian Randomization to link specific gut bacteria to premature rupture of membranes (PROM). Certain bacteria may reduce PROM risk, while others increase it, offering new diagnostic and therapeutic targets.
Area of Science:
- Microbiome research
- Reproductive health
- Genetics
Background:
- Gut microbiota composition is increasingly linked to maternal pregnancy outcomes.
- The precise causal role of gut microbiota in premature rupture of membranes (PROM) requires further investigation.
Purpose of the Study:
- To investigate the potential causal relationship between gut microbiota and the risk of premature rupture of membranes (PROM) using a two-sample Mendelian Randomization (MR) approach.
Main Methods:
- Utilized large-scale genome-wide association study (GWAS) data for gut microbiota (n=14,306) and PROM (3011 cases, 104247 controls).
- Employed various MR methods, including Inverse Variance Weighted (IVW), MR-Egger, and weighted median, to assess causal associations.
- Conducted sensitivity analyses to ensure the robustness and validity of the findings, including MR-Egger intercept tests and Cochran's Q tests.
Main Results:
- Identified specific gut bacteria associated with PROM risk: *class Mollicutes*, *genus Marvinbryantia*, *genus Ruminooccaceae UCG003*, and *phylum Tenericutes* were linked to reduced PROM risk.
- *Genus Collinsella*, *genus Intestinibacter*, and *genus Turicibacter* were associated with an increased risk of PROM.
- Sensitivity analyses indicated no significant horizontal pleiotropy or heterogeneity for most identified microbiota, though *genus Lachnoclostridium* was excluded due to potential pleiotropy.
Conclusions:
- Established a potential causal link between specific gut microbiota compositions and the risk of PROM.
- Findings suggest that certain gut bacteria may act as probiotics or pathogens influencing PROM development.
- Highlights a novel avenue for PROM diagnosis, treatment, and clinical prevention strategies targeting the gut microbiome.
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