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Updated: Jun 22, 2025
Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment
Published on: November 17, 2018
Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study
Liu-Dan Liang1,2,3,4, Sheng Li2,5, Mei-Jin Huang2,3
1Department of Cardiology, The First Clinical Medical College of Jinan University, Guangzhou, China.
Background:
Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis.
Methods:
This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings.
Results:
Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011).
Conclusion:
This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.
Insights
This study investigated the causal link between gut microbiota and puerperal sepsis (PS) using Mendelian randomization. Certain gut bacteria, like Lachnospiraceae, may reduce PS risk, while Ruminococcaceae might increase it.
Area of Science:
- Microbiome research
- Maternal health
- Infectious disease epidemiology
Background:
- Observational studies suggest a link between gut microbiota and puerperal sepsis (PS).
- Previous research has not established a causal relationship between gut microbiota and PS.
- Puerperal sepsis remains a significant concern in maternal healthcare.
Purpose of the Study:
- To determine a potential causal association between gut microbiota composition and puerperal sepsis (PS).
- To utilize a two-sample Mendelian randomization (MR) analysis for investigating causality.
- To identify specific gut microbial species that may influence PS risk.
Main Methods:
- Performed a two-sample Mendelian randomization (MR) analysis.
- Utilized publicly available genome-wide association study (GWAS) summary data for gut microbiota (n=18,340) and PS (3,940 cases, 202,267 controls).
- Employed the inverse variance weighted (IVW) method as the primary analysis, supported by sensitivity analyses (MR-Egger, MR-PRESSO, Cochran's Q, leave-one-out).
Main Results:
- Identified three gut microbial species associated with PS risk.
- Lachnospiraceae FCS020 showed a potential protective effect, reducing PS risk by approximately 19% (OR=0.81, p=0.047).
- Lachnospiraceae NK4A136 also suggested a reduced risk of PS (OR=0.80, p=0.024).
- Ruminococcaceae NK4A214 was positively associated with an increased risk of PS (OR=1.33, p=0.011).
Conclusions:
- This MR study provides novel evidence for both beneficial and detrimental causal effects of gut microbiota on puerperal sepsis risk.
- Findings suggest specific gut bacteria may play a role in the pathogenesis of PS.
- Potential implications for developing microbiota-targeted prevention and treatment strategies for PS.
