Summary:
The gut microbiome has been linked to several cardiometabolic conditions including obesity, diabetes, and cardiovascular disease (CVD). Observational and cohort studies have identified differences in microbial composition and diversity in individuals with CVD, as well as associations with key risk factors such as blood lipids. Several microbial metabolic pathways may contribute to these associations. For example, gut bacteria can convert dietary nutrients into compounds such as trimethylamine N-oxide (TMAO), which has been associated with increased cardiovascular risk. Microbial activity also influences bile acid metabolism and cholesterol regulation, both of which are important for overall cardiometabolic health. This study is an observational cohort study using data from the Framingham Heart Study and investigated the relationship between the gut microbiome, microbial metabolism, and cardiovascular health using analyses of stool samples. The analysis identified numerous associations between microbial species and metabolic features. A key finding was that species from the Oscillibacter genus which is a group of bacteria that resides within the human gut, were associated with lower cholesterol levels in both stool and blood. Further experimental analysis showed that these bacteria can take up and metabolise cholesterol into other compounds, indicating an ability to modify cholesterol. Overall, this study suggests that specific gut microbes may influence cardiovascular health through their metabolic activity, particularly cholesterol metabolism.
Abstract:
Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.
Article Publication Date: 11/04/2024
DOI: 10.1016/j.cell.2024.03.014
