Sex-specific differences in intestinal microbiota associated with cardiovascular diseases
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Garcia-Fernandez H, Arenas-de Larriva AP, Lopez-Moreno J, Gutierrez-Mariscal FM, Romero-Cabrera JL, Molina-Abril H, Torres-Peña JD, Rodriguez-Cano D, Malagon MM, Ordovas JM, Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Camargo A
Journal
Biology of sex differences
Year
2024
Keywords:
CORDIOPREV, Cardiovascular diseases, Dysbiosis, Gut microbiota, Sexual dimorphism
BACKGROUND: Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women afflicted with CHD and delineate these against a non-CVD control group for each sex. METHODS: Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our findings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software. RESULTS: Our results showed a sex-specific variation (beta diversity) in the intestinal microbiota, while alpha-biodiversity remained consistent across both sexes. Linear discriminant analysis effect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identified seven bacterial taxa-g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)-as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-afflicted and non-CVD individuals, when analyzed separately by sex. CONCLUSION: Our findings suggest a sex-specific dysbiosis in the intestinal microbiota linked to CHD, potentially contributing to the sex disparity observed in CVD incidence. Trial registration Clinical Trials.gov.Identifier NCT00924937. The frequency with which cardiovascular diseases occur differs in men and women as it appears with greater frequency in men. Moreover, it has been known for years that the community of bacteria living in our intestine, also known as the gut microbiota, influences the development of these diseases. Indeed, nowadays it known the influence of the intestinal microbiota in the development of atherosclerosis, the pathological process which is responsible for the three main causes of cardiovascular diseases: coronary heart disease, cerebrovascular disease and peripheral arterial disease. This study shows the differences in the community of bacteria living in the gut of men and those living in the gut of women, so that these differences could explain, at least in part, the differences in the frequency with which cardiovascular diseases appear between men and women. Our results suggest that the dysbiosis of the intestinal microbiota associated with CHD seems to be partially sex-specific, which may influence the sexual dimorphism in its incidence. Moreover, the identification of the mechanisms responsible for sexual dimorphism in the incidence of metabolic and cardiovascular disease is of particular importance when developing effective strategies and therapies aimed at reducing their incidence and recurrence. Indeed, the strategies and therapies used to treat the dysbiosis of the gut microbiota should be sex-specific.
Experiment 1
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Subjects
- Location of subjects
- Spain
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Cardiovascular disease [X]Cardiovascular disease, unspecified,[X]Cardiovascular disease, unspecified (disorder),[X]Other forms of heart disease,[X]Other forms of heart disease (disorder),[X]Other ill-defined heart diseases,[X]Other ill-defined heart diseases (disorder),[X]Other specified diseases of pericardium,[X]Other specified diseases of pericardium (disorder),ASCVD,CARDIOVASC DIS,cardiovascular disease,Cardiovascular Disease (CVD),cardiovascular disease (CVD),Cardiovascular disease, NOS,Cardiovascular disease, unspecified,Cardiovascular Diseases,Cardiovascular Disorder,cardiovascular disorder,Cardiovascular disorder, NOS,Cardiovascular Disorders,Cardiovascular system disease,cardiovascular system disease,cardiovascular system disease or disorder,Certain sequelae of myocardial infarction, not elsewhere classified,CIRCULATORY DISEASE NOS,circulatory system disease,Circulatory system disease NOS,Circulatory system disease NOS (disorder),CVD,CVD, NOS,CVS disease,Disease affecting entire cardiovascular system,Disease affecting entire cardiovascular system (disorder),Disease of cardiovascular system,disease of cardiovascular system,Disease of cardiovascular system (disorder),Disease of cardiovascular system, NOS,disease of subdivision of hemolymphoid system,disease or disorder of cardiovascular system,Disease, Cardiovascular,DISEASES OF THE CIRCULATORY SYSTEM,Diseases, Cardiovascular,Disorder of cardiovascular system,disorder of cardiovascular system,Disorder of cardiovascular system (disorder),Disorder of circulatory system,Disorder of circulatory system, NOS,Disorder of the circulatory system,Ill-defined descriptions and complications of heart disease,ILL-DEFINED HRT DIS NEC,Other diseases of endocardium,Other diseases of endocardium (disorder),Other diseases of pericardium,Other diseases of pericardium (disorder),Other disorders of papillary muscle,Other forms of heart disease,Other forms of heart disease (disorder),Other heart disease,Other heart disease (disorder),Other heart disease NOS,Other heart disease NOS (disorder),Other ill-defined heart disease,Other ill-defined heart disease (disorder),Other ill-defined heart disease NOS,Other ill-defined heart disease NOS (disorder),Other ill-defined heart diseases,Other pericardial disease NOS,Other pericardial disease NOS (disorder),OTHER SEQUELAE OF MI NEC,Other sequelae of myocardial infarction, not elsewhere classified,Other specified diseases of pericardium,Other specified pericardial disease NOS,Other specified pericardial disease NOS (disorder),PAPILLARY MUSCLE DIS NEC,PERICARDIAL DISEASE NEC,Unspecified circulatory system disorder,Cardiovascular disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Men with coronary heart disease (CHD)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Women with coronary heart disease (CHD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Women with coronary heart disease, and enrolled in the CORDIOPREV study.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 567
- Group 1 sample size Number of subjects in the case (exposed) group
- 112
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 1 month
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Fig.1 B
Description: Differently abundant taxa in CHD patients according to the sex, based on LEfSe analysis.
Abundance in Group 1: decreased abundance in Women with coronary heart disease (CHD)
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Fig.1 B
Description: Differently abundant taxa in CHD patients according to sex, based on LEfSe analysis.
Abundance in Group 1: increased abundance in Women with coronary heart disease (CHD)
Revision editor(s): Andre
Experiment 2
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Men without cardiovascular disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Women without cardiovascular disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Women without cardiovascular disease, and enrolled in the ONCOVER study
- Group 0 sample size Number of subjects in the control (unexposed) group
- 242
- Group 1 sample size Number of subjects in the case (exposed) group
- 87
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Fig. 2 B
Description: Differently abundant taxa in non‑CVD patients according to sex, based on LEfSe analysis
Abundance in Group 1: decreased abundance in Women without cardiovascular disease
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidales | ||
| Bacteroidia | ||
| Bacteroidota | ||
| Collinsella | ||
| Coriobacteriaceae |
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Fig. 2 B
Description: Differently abundant taxa in non‑CVD patients according to sex, based on LEfSe analysis
Abundance in Group 1: increased abundance in Women without cardiovascular disease
Revision editor(s): Andre
Experiment 3
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Men with coronary heart disease (CHD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Men with coronary heart disease, and enrolled in the CORDIOPREV study.
- Group 1 sample size Number of subjects in the case (exposed) group
- 567
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Fig. 4
Description: Linear discriminant analysis between CHD patients and non‑CVD subjects in Men
Abundance in Group 1: increased abundance in Men with coronary heart disease (CHD)
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Figure 4
Description: Linear discriminant analysis between CHD patients and non‑CVD subjects in Men
Abundance in Group 1: decreased abundance in Men with coronary heart disease (CHD)
Experiment 4
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Women without cardiovascular disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Women with coronary heart disease (CHD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Women with coronary heart disease, and enrolled in the CORDIOPREV study
- Group 0 sample size Number of subjects in the control (unexposed) group
- 87
- Group 1 sample size Number of subjects in the case (exposed) group
- 112
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Figure 4
Description: Linear discriminant analysis between CHD patients and non‑CVD subjects in Women
Abundance in Group 1: increased abundance in Women with coronary heart disease (CHD)
Revision editor(s): Andre
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-25
Source: Figure 4
Description: Linear discriminant analysis between CHD patients and non‑CVD subjects in Women
Abundance in Group 1: decreased abundance in Women with coronary heart disease (CHD)
Revision editor(s): Andre
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