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Updated: Sep 15, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Plasma Sphingomyelin Levels Mediate the Causal Relationship Between Gut Microbiota and Myocardial Interstitial
Mingjun Yu1,2, Xingxiao Huang1,2, Beibei Gao1,2
1School of Medicine, Zhejiang University, Hangzhou, 310006, China.
Background:
Prior studies established associations between gut microbiota and myocardial interstitial fibrosis. Nevertheless, the causal relationships and potential intermediaries remain unknown. Thus, we employed a Mendelian randomization strategy to explore whether gut microbiota causally influence myocardial interstitial fibrosis and to assess whether plasma metabolites serve as potential intermediaries in this pathway.
Methods:
A two-sample Mendelian randomization approach was performed, utilizing genome-wide association studies to examine the causal relationship between gut microbiota (n= 18,340) and myocardial interstitial fibrosis (n=41,505). Additionally, an investigation was conducted to determine the potential mediation by four plasma metabolites (n=8,299) via a two-step Mendelian randomization analysis. Inverse variance weighted method was the primary method employed in Mendelian randomization, and complementary analyses were conducted alongside to enhance the robustness of the results.
Results:
Mendelian randomization analysis indicated suggestive associations of three microbial taxa with myocardial interstitial fibrosis. The most significant taxon was the genus Faecalibacterium (β [SE], -0.1272 [0.0347], P = 0.0002). Reverse Mendelian randomization analyses revealed no evidence of myocardial interstitial fibrosis affecting these three microbial taxa. In the two-step Mendelian randomization analysis involving four plasma metabolites, it was found that plasma sphingomyelin levels mediated the causal effects of genus Faecalibacterium on myocardial interstitial fibrosis (proportion mediated = 14.2%, 95% CI = 1.4-27.0%).
Conclusion:
The study validates the causality between particular gut microbial taxa and myocardial interstitial fibrosis, and suggests that plasma sphingomyelin might mediate this association. These findings offer a novel perspective on myocardial interstitial fibrosis prevention, and underscore the significance of plasma sphingomyelin in human health and disease.
Insights
Gut bacteria, specifically genus Faecalibacterium, may causally influence myocardial interstitial fibrosis. Plasma sphingomyelin levels appear to mediate this relationship, offering new insights into heart health.
Area of Science:
- Genetics
- Microbiology
- Cardiology
Background:
- Previous research suggests links between gut microbiota and myocardial interstitial fibrosis.
- Causal relationships and intermediary factors remain unclear.
Purpose of the Study:
- To investigate the causal effect of gut microbiota on myocardial interstitial fibrosis using Mendelian randomization.
- To identify potential plasma metabolite intermediaries in this pathway.
Main Methods:
- Two-sample Mendelian randomization utilizing genome-wide association studies (GWAS) for gut microbiota (n=18,340) and myocardial interstitial fibrosis (n=41,505).
- Two-step Mendelian randomization to assess mediation by four plasma metabolites (n=8,299).
- Primary analysis employed the inverse variance weighted (IVW) method with complementary analyses for robustness.
Main Results:
- Suggestive causal associations were found between three microbial taxa and myocardial interstitial fibrosis, with genus Faecalibacterium being most significant (P = 0.0002).
- Reverse Mendelian randomization showed no evidence of myocardial interstitial fibrosis affecting these taxa.
- Plasma sphingomyelin levels mediated 14.2% of the causal effect of genus Faecalibacterium on myocardial interstitial fibrosis.
Conclusions:
- This study provides evidence for a causal link between specific gut microbes and myocardial interstitial fibrosis.
- Plasma sphingomyelin is identified as a potential mediator in this association.
- Findings highlight novel avenues for myocardial interstitial fibrosis prevention and the importance of sphingomyelin.
