Multiomics reveals gut dysbiosis contributes to fatty acid dysmetabolism in early phase of acute myocardial infarction
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Curated by eLife
eLife assessment
This study provides valuable information about the microbiome and metabolome, and their correlation with acute myocardial infarction. However, the relationship established between these variables is limited to a correlation, and therefore the strength of the evidence is incomplete.
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Abstract
Acute myocardial infarction (AMI) remains a major cause of death, with limited understanding of its early risk stratification. While late-stage AMI has recognized associations with gut microbiome disturbances, the connection to eAMI is less explored.Using metabolomics and metagenomics, we analyzed 56 samples, comprising 30 eAMI patients (within 12 hours of onset) and 26 age- and gender-matched healthy controls, to discern the influence of gut microbes and their metabolites.We found the eAMI plasma is dominated by increased long-chain fatty acids (LCFAs), 14 of which provide differentiating power of eAMI patients from HCs. Multiomics analysis reveals up to 70% of the variance in LCFAs of eAMI patients can be explained by altered gut microbiome. Higher-resolution profiling of gut bacterial species demonstrated that bacterial structural variations are mechanistically linked to LCFAs dysregulation. By in silico molecular docking and in vitro thrombogenic assay in isolated human platelets, we highlighted that eAMI-associated LCFAs contribute to platelet aggregation, a driving factor for AMI initiation.LCFAs hold significant potential as early biomarkers of AMI and gut microbiome contributes to altered LCFAs in eAMI. Further studies are imperative to expand upon these observations to better leverage LCFAs as a potential biomarker for eAMI and as a therapeutic target for inhibition of platelet aggregation in eAMI.
Article activity feed
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Author Response:
Reviewer #1 (Public Review):
Summary:
The authors aimed to identify potential biomarkers for acute myocardial infarction (AMI) through blood metabolomics and fecal microbiome analysis. They found that long chain fatty acids (LCFAs) could serve as biomarkers for AMI and demonstrated a correlation between LCFAs and the gut microbiome. Additionally, in silico molecular docking and in vitro thrombogenic assays showed that these LCFAs can induce platelet aggregation.
Strengths:
The study utilized a comprehensive approach combining blood metabolomics and fecal microbiome analysis.
The findings suggest a novel use of LCFAs as biomarkers for AMI.
The correlation between LCFAs and the gut microbiome is a significant contribution to understanding the interplay between gut health and heart disease.
The use of in silico and in …
Author Response:
Reviewer #1 (Public Review):
Summary:
The authors aimed to identify potential biomarkers for acute myocardial infarction (AMI) through blood metabolomics and fecal microbiome analysis. They found that long chain fatty acids (LCFAs) could serve as biomarkers for AMI and demonstrated a correlation between LCFAs and the gut microbiome. Additionally, in silico molecular docking and in vitro thrombogenic assays showed that these LCFAs can induce platelet aggregation.
Strengths:
The study utilized a comprehensive approach combining blood metabolomics and fecal microbiome analysis.
The findings suggest a novel use of LCFAs as biomarkers for AMI.
The correlation between LCFAs and the gut microbiome is a significant contribution to understanding the interplay between gut health and heart disease.
The use of in silico and in vitro assays provides mechanistic insights into how LCFAs may influence platelet aggregation.
Weaknesses:
The evidence is incomplete as it does not definitively prove that gut dysbiosis contributes to fatty acid dysmetabolism.
We appreciate this reviewer’s insightful comment regarding the causal relationship between gut dysbiosis and fatty acid dysmetabolism. We acknowledge that our study primarily demonstrates a strong association rather than causation. While establishing causality was beyond the scope of the current study, we recognize the importance of addressing this point. In our revised manuscript, we will emphasize the observational nature of our findings and discuss the need for future research, including longitudinal studies and interventional trials, to explore the causal links between gut dysbiosis and fatty acid dysmetabolism. We believe that this clarification strengthens the interpretation of our results and aligns with the reviewer's concern.
The study primarily shows an association between the gut microbiome and fatty acid metabolism without establishing causation.
We agree with the reviewer that our study presents an association rather than definitive proof of causation between the gut microbiome and fatty acid metabolism. To address this, we plan to expand the discussion section to more clearly outline the limitations of our study in establishing causality. We will also propose future research directions, such as the use of animal models and longitudinal human studies, which could help elucidate the causal pathways. By clarifying this aspect, we aim to provide a more balanced perspective on our findings.
Reviewer #2 (Public Review):
Summary:
Fan et al. investigated the relationship between early acute myocardial infarction (eAMI) and disturbances in the gut microbiome using metabolomics and metagenomics analyses. They studied 30 eAMI patients and 26 healthy controls, finding elevated levels of long-chain fatty acids (LCFA) in the plasma of eAMI patients.
Strengths:
The research attributed a substantial portion of LCFA variance in eAMI to changes in the gut microbiome, as indicated by omics analyses. Computational profiling of gut bacteria suggested structural variations linked to LCFA variance. The authors also conducted molecular docking simulations and platelet assays, revealing that eAMI-associated LCFAs may enhance platelet aggregation.
Weaknesses:
The results should be validated using different assays, and animal models should be considered to explore the mechanisms of action.
We appreciate the reviewer’s suggestion to validate our findings using additional assays and animal models. We agree that further validation is crucial to confirm the robustness of our results and to explore the underlying mechanisms in greater detail. While our current study focused on human subjects and in vitro assays to establish initial findings, we acknowledge that additional experimental approaches are necessary. In the revised manuscript, we plan to include a discussion on the potential use of different assays (e.g., advanced metabolomics techniques, multi-omics integration) and animal models to validate and expand upon our findings. Moreover, we are planning to undertake these experiments in future studies to build upon the foundational work presented here.
We believe that our revised responses and the planned manuscript revisions will address the reviewers’ concerns effectively. We are confident that these changes will enhance the overall contribution of our study to the field. Thank you again for your valuable feedback.
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eLife assessment
This study provides valuable information about the microbiome and metabolome, and their correlation with acute myocardial infarction. However, the relationship established between these variables is limited to a correlation, and therefore the strength of the evidence is incomplete.
-
Reviewer #1 (Public Review):
Summary:
The authors aimed to identify potential biomarkers for acute myocardial infarction (AMI) through blood metabolomics and fecal microbiome analysis. They found that long chain fatty acids (LCFAs) could serve as biomarkers for AMI and demonstrated a correlation between LCFAs and the gut microbiome. Additionally, in silico molecular docking and in vitro thrombogenic assays showed that these LCFAs can induce platelet aggregation.
Strengths:
The study utilized a comprehensive approach combining blood metabolomics and fecal microbiome analysis.
The findings suggest a novel use of LCFAs as biomarkers for AMI.
The correlation between LCFAs and the gut microbiome is a significant contribution to understanding the interplay between gut health and heart disease.
The use of in silico and in vitro assays provides …
Reviewer #1 (Public Review):
Summary:
The authors aimed to identify potential biomarkers for acute myocardial infarction (AMI) through blood metabolomics and fecal microbiome analysis. They found that long chain fatty acids (LCFAs) could serve as biomarkers for AMI and demonstrated a correlation between LCFAs and the gut microbiome. Additionally, in silico molecular docking and in vitro thrombogenic assays showed that these LCFAs can induce platelet aggregation.
Strengths:
The study utilized a comprehensive approach combining blood metabolomics and fecal microbiome analysis.
The findings suggest a novel use of LCFAs as biomarkers for AMI.
The correlation between LCFAs and the gut microbiome is a significant contribution to understanding the interplay between gut health and heart disease.
The use of in silico and in vitro assays provides mechanistic insights into how LCFAs may influence platelet aggregation.
Weaknesses:
The evidence is incomplete as it does not definitively prove that gut dysbiosis contributes to fatty acid dysmetabolism.
The study primarily shows an association between the gut microbiome and fatty acid metabolism without establishing causation.
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Reviewer #2 (Public Review):
Summary:
Fan et al. investigated the relationship between early acute myocardial infarction (eAMI) and disturbances in the gut microbiome using metabolomics and metagenomics analyses. They studied 30 eAMI patients and 26 healthy controls, finding elevated levels of long-chain fatty acids (LCFA) in the plasma of eAMI patients.
Strengths:
The research attributed a substantial portion of LCFA variance in eAMI to changes in the gut microbiome, as indicated by omics analyses. Computational profiling of gut bacteria suggested structural variations linked to LCFA variance. The authors also conducted molecular docking simulations and platelet assays, revealing that eAMI-associated LCFAs may enhance platelet aggregation.
Weaknesses:
The results should be validated using different assays, and animal models should be …
Reviewer #2 (Public Review):
Summary:
Fan et al. investigated the relationship between early acute myocardial infarction (eAMI) and disturbances in the gut microbiome using metabolomics and metagenomics analyses. They studied 30 eAMI patients and 26 healthy controls, finding elevated levels of long-chain fatty acids (LCFA) in the plasma of eAMI patients.
Strengths:
The research attributed a substantial portion of LCFA variance in eAMI to changes in the gut microbiome, as indicated by omics analyses. Computational profiling of gut bacteria suggested structural variations linked to LCFA variance. The authors also conducted molecular docking simulations and platelet assays, revealing that eAMI-associated LCFAs may enhance platelet aggregation.
Weaknesses:
The results should be validated using different assays, and animal models should be considered to explore the mechanisms of action.
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