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Roles of Gut Microbiota and Associated Metabolites in Clostridioides difficile Infection Cover

Roles of Gut Microbiota and Associated Metabolites in Clostridioides difficile Infection

Polish Journal of Microbiology
Volume 74 (2025): Issue 2 (June 2025)
By: YAN GAO,  JINGXIN MA,  KEDI WANG,  KAIHUI MA,  WEN ZHAO,  JIANRONG SU and  LIYAN MA  
Open Access
|Jun 2025

Figures & Tables

Fig. 1.

Assumptions and design of the bidirectional mediation Mendelian randomization (MR) analysis. Firstly, a two-sample bidirectional MR was performed to investigate the causal relationships between gut microbiota (exposures) and Clostridioides difficile infection (outcomes). Secondly, 1,400 blood metabolites (mediator) were selected for subsequent mediation analysis. Finally, a two-step MR analysis was conducted to detect potential mediating metabolites (Step 1, the effect of gut microbiota on metabolites; Step 2, the effect of metabolites on CDI). LDSC – linkage disequilibrium score regression; CLSA – Canadian Longitudinal Study on Aging; IVW – inverse variance weighted; CDI – C. difficile infection
Assumptions and design of the bidirectional mediation Mendelian randomization (MR) analysis. Firstly, a two-sample bidirectional MR was performed to investigate the causal relationships between gut microbiota (exposures) and Clostridioides difficile infection (outcomes). Secondly, 1,400 blood metabolites (mediator) were selected for subsequent mediation analysis. Finally, a two-step MR analysis was conducted to detect potential mediating metabolites (Step 1, the effect of gut microbiota on metabolites; Step 2, the effect of metabolites on CDI). LDSC – linkage disequilibrium score regression; CLSA – Canadian Longitudinal Study on Aging; IVW – inverse variance weighted; CDI – C. difficile infection

Fig. 2.

Circular heatmap of suggestive genetic correlation between gut microbes and Clostridioides difficile infection.
Circular heatmap of suggestive genetic correlation between gut microbes and Clostridioides difficile infection.

Fig. 3.

Suggestive causal effects of Proteobacteria on Clostridioides difficile infection (CDI). A) MR results of casual association between gut microbes belonging to Proteobacteria and CDI; B) Significant casual estimates from genetically predicted Proteobacteria to CDI. MR – Mendelian randomization; OR – odds ratio
Suggestive causal effects of Proteobacteria on Clostridioides difficile infection (CDI). A) MR results of casual association between gut microbes belonging to Proteobacteria and CDI; B) Significant casual estimates from genetically predicted Proteobacteria to CDI. MR – Mendelian randomization; OR – odds ratio

Detailed information of studies and datasets used for analysis_

Data sourcePhenotypeSample sizeCasesPopulation
Dutch MicrobiomeGut microbial7,738/Netherlands
European subjects in CLSAMetabolites8,299/European
FinnGen R10CDI409,4323,384European

Metabolites as intermediates in causal effects of gut microbiota on Clostridioides difficile infection (CDI)_

Exposureβe-iORe-iPe-iIntermediateβi-oORi-oPi-oOutcomeβe-oORe-o
o_Burkholderiales–0.1100.8960.0473-hydroxylaurate–0.6160.5400.010CDI0.2201.247
DOI: https://doi.org/10.33073/pjm-2025-017 | Journal eISSN: 2544-4646 | Journal ISSN: 1733-1331
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Language: English
Page range: 206 - 217
Submitted on: Dec 31, 2024
Accepted on: Apr 25, 2025
Published on: Jun 18, 2025
Published by: Polish Society of Microbiologists
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
infection,
Proteobacteria,
metabolites,
Mendelian randomization,
linkage disequilibrium score regression
Related subjects:
Life sciences,
Microbiology and virology

© 2025 YAN GAO, JINGXIN MA, KEDI WANG, KAIHUI MA, WEN ZHAO, JIANRONG SU, LIYAN MA, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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