Sex-specific differences in intestinal microbiota associated with cardiovascular disease

Authors: GARCIA-FERNANDEZ, HELENA - Maimonides Biomedical Research Institute Of Cordoba (IMIBIC); ARENAS-DE LARRIVA, ANTONIO - Universidad De Cordoba; LOPEZ-MORENO, JAVIER - Universidad De Cordoba; GUTIERREZ MARISCAL, FRANCISCO - Universidad De Cordoba; ROMERO CABRERA, JUAN - Universidad De Cordoba; MOLINA-ABRIL, HELENA - University Of Seville; TORRES PENA, JOSE - Universidad De Cordoba; RODRIGUEZ-CANO, DIEGO - University Hospital Reina Sofia; MALAGON, MARIA - Universidad De Cordoba; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DELGADO LISTA, JAVIER - Universidad De Cordoba; PEREZ MARTINEZ, PABLO - Universidad De Cordoba; LOPEZ MIRANDA, JOSE - Universidad De Cordoba; CAMARGO, ANTONIO - Maimonides Biomedical Research Institute Of Cordoba (IMIBIC)

Submitted to: Biology of Sex Differences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2024
Publication Date: 1/19/2024
Citation: Garcia-Fernandez, H., Arenas-De Larriva, A.P., Lopez-Moreno, J., Gutierrez Mariscal, F., Romero Cabrera, J.L., Molina-Abril, H., Torres Pena, J.D., Rodriguez-Cano, D., Malagon, M.M., Ordovas, J.M., Delgado Lista, J., Perez Martinez, P., Lopez Miranda, J., Camargo, A. 2024. Sex-specific differences in intestinal microbiota associated with cardiovascular disease. Biology of Sex Differences. https://doi.org/10.1186/s13293-024-00582-7.
DOI: https://doi.org/10.1186/s13293-024-00582-7

Interpretive Summary: Cardiovascular diseases display a higher prevalence in men than women. To understand the underlying mechanisms of this disparity, gut bacteria were compared between men and women with heart disease, and then compared to people without heart disease. The types of bacteria in the gut vary between men and women and can indicate the presence of heart disease. This work helps understand why more men get heart disease than women and points to the importance of gut health in heart disease.

Technical Abstract: 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.