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Roles of Gut Microbiota and Associated Metabolites in Clostridioides difficile Infection

YAN GAO

YAN GAO

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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GAO, YAN
, 
JINGXIN MA

JINGXIN MA

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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MA, JINGXIN
, 
KEDI WANG

KEDI WANG

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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WANG, KEDI
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KAIHUI MA

KAIHUI MA

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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MA, KAIHUI
, 
WEN ZHAO

WEN ZHAO

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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ZHAO, WEN
, 
JIANRONG SU

JIANRONG SU

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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SU, JIANRONG
 y 
LIYAN MA

LIYAN MA

Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China
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MA, LIYAN
  
18 jun 2025
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Categoría del artículo: Original Paper
Publicado en línea: 18 jun 2025
Páginas: 206 - 217
Recibido: 31 dic 2024
Aceptado: 25 abr 2025
DOI: https://doi.org/10.33073/pjm-2025-017
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© 2025 YAN GAO et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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 source Phenotype Sample size Cases Population
Dutch Microbiome Gut microbial 7,738 / Netherlands
European subjects in CLSA Metabolites 8,299 / European
FinnGen R10 CDI 409,432 3,384 European

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

Exposure βe-i ORe-i Pe-i Intermediate βi-o ORi-o Pi-o Outcome βe-o ORe-o
o_Burkholderiales –0.110 0.896 0.047 3-hydroxylaurate –0.616 0.540 0.010 CDI 0.220 1.247
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Ciencias de la vida, Microbiología y virología
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