Abstract
Background/Objectives: Cardiovascular diseases remain the leading cause of global mortality, with the gut microbiome emerging as a critical factor. This study aimed to characterize gut microbiome composition and metabolic pathways in individuals with low cardiovascular risk (LCR) compared to healthy controls to reveal insights into early disease shifts. Methods: We performed shotgun metagenomic sequencing on fecal samples from 25 LCR individuals and 25 matched healthy controls. Participants underwent a comprehensive cardiovascular evaluation. Taxonomic classification used MetaPhlAn 4, and functional profiling employed HUMAnN 3. Results: Despite similar alpha diversity, significant differences in bacterial community structure were observed between groups (PERMANOVA, p < 0.05). The LCR group showed enrichment of Faecalibacterium prausnitzii (p = 0.035), negatively correlating with atherogenic markers, including ApoB (r = -0.3, p = 0.025). Conversely, Fusicatenibacter saccharivorans positively correlated with ApoB (r = 0.4, p = 0.006). Metabolic pathway analysis revealed upregulation of nucleotide biosynthesis, glycolysis, and sugar degradation pathways in the LCR group, suggesting altered metabolic activity. Conclusions: We identified distinct gut microbiome signatures in LCR individuals that may represent early alterations associated with cardiovascular disease development. The opposing correlations between F. prausnitzii and F. saccharivorans with lipid parameters highlight their potential roles in cardiometabolic health. These findings suggest gut microbiome signatures may serve as indicators of early metabolic dysregulation preceding clinically significant cardiovascular disease.