A study of the gut microbiome in individuals with atherosclerotic cardiovascular disease (ACVD) and healthy controls reveals significant differences in microbial composition and function. The ACVD gut microbiome showed increased abundance of Enterobacteriaceae and Streptococcus spp., and reduced abundance of Bacteroides and Prevotella. Functional analysis indicated a shift towards metabolism and transport of molecules important for cardiovascular health. The study used metagenome-wide association studies (MWAS) on stool samples from 218 ACVD patients and 187 healthy controls, identifying 536 microbial strains (metagenomic linkage groups, MLGs) that differed in abundance between the groups. These MLGs were associated with various clinical features, including blood pressure, lipid levels, and markers of inflammation. The study also found that the gut microbiome of ACVD patients was less fermentative and more inflammatory compared to healthy individuals, with reduced potential for biosynthesis of vitamins and increased potential for metabolism of certain molecules. The gut microbiome of ACVD patients was also enriched in virulence factors and showed altered lipid metabolism. The study highlights the role of the gut microbiome in the development and progression of ACVD and other cardiometabolic diseases. The findings suggest that the gut microbiome could serve as a potential biomarker for ACVD and other related diseases. The study also identified that drug use may influence the gut microbiome, but ACVD status was the major distinguishing feature in the cohort. The study provides a comprehensive resource for further research on the role of the gut microbiome in ACVD and other diseases.A study of the gut microbiome in individuals with atherosclerotic cardiovascular disease (ACVD) and healthy controls reveals significant differences in microbial composition and function. The ACVD gut microbiome showed increased abundance of Enterobacteriaceae and Streptococcus spp., and reduced abundance of Bacteroides and Prevotella. Functional analysis indicated a shift towards metabolism and transport of molecules important for cardiovascular health. The study used metagenome-wide association studies (MWAS) on stool samples from 218 ACVD patients and 187 healthy controls, identifying 536 microbial strains (metagenomic linkage groups, MLGs) that differed in abundance between the groups. These MLGs were associated with various clinical features, including blood pressure, lipid levels, and markers of inflammation. The study also found that the gut microbiome of ACVD patients was less fermentative and more inflammatory compared to healthy individuals, with reduced potential for biosynthesis of vitamins and increased potential for metabolism of certain molecules. The gut microbiome of ACVD patients was also enriched in virulence factors and showed altered lipid metabolism. The study highlights the role of the gut microbiome in the development and progression of ACVD and other cardiometabolic diseases. The findings suggest that the gut microbiome could serve as a potential biomarker for ACVD and other related diseases. The study also identified that drug use may influence the gut microbiome, but ACVD status was the major distinguishing feature in the cohort. The study provides a comprehensive resource for further research on the role of the gut microbiome in ACVD and other diseases.