Gut microbial community structure, metabolic signature, and resistome in dyslipidemia: implications for...

Dyslipidemia, characterized by abnormal blood lipid levels, constitutes a significant risk factor for cardiovascular disease. Emerging evidence indicates that the gut microbiota influences lipid metabolism, although findings across studies have been inconsistent. In this cross-sectional investigation, we analyzed the composition of gut microbiota, associated metabolic pathways, predicted gut metabolites, and the resistome in 1,384 participants (including 895 individuals with dyslipidemia and 489 controls) through shotgun metagenomic sequencing. Our findings demonstrated that Bacteroides caccae was enriched among dyslipidemia cases, potentially contributing to inflammation and altered lipid metabolism. Conversely, Coprococcus eutactus and Coprococcus catus, recognized producers of short-chain fatty acids (SCFAs) involved in lipid regulation, as well as Blautia obeum, known to be positively affected by SCFAs, were more prevalent in the control group. Additionally, we identified an enrichment of the gene family responsible for dTDP-beta-D-fucofuranose biosynthesis, associated with bacterial pathogenicity, in dyslipidemia cases, with Bacteroides stercoris serving as a major contributor. Dyslipidemia cases also exhibited depletion of glycogen and peptidoglycan biosynthesis pathways, which may compromise energy storage and immune function, alongside decreased levels of pseudouridine, a molecule involved in RNA metabolism. Furthermore, a marginal increase in abundance of antibiotic-resistance genes, tetQ, was observed in dyslipidemia cases, suggesting a potential link between the gut resistome and metabolic dysregulation. These results offer novel insights into the role of gut microbiota in the pathophysiology of dyslipidemia and underscore potential microbiome-targeted interventions for metabolic disease management.IMPORTANCEDyslipidemia, characterized by abnormal blood lipid levels, is a significant risk factor for cardiovascular disease. Emerging evidence suggests that the gut microbiota plays a role in lipid metabolism, although findings across studies have varied. This study analyzed the gut microbiota, metabolic pathways, predicted gut metabolites, and antimicrobial resistance genes in 1,384 participants using shotgun metagenomic sequencing. Individuals with dyslipidemia exhibited an imbalance in gut bacteria, including an increase in Bacteroides caccae, a species associated with inflammation, and a decrease in short-chain fatty acid-producing bacteria such as Coprococcus eutactus and Blautia obeum, which support metabolic health. Furthermore, we identified significant changes in microbial metabolic pathways related to energy storage and immune function, as well as an increased abundance of tetracycline resistance genes (tetQ), suggesting a potential link between dyslipidemia and antimicrobial resistance. Our study provides a comprehensive overview of dyslipidemia-associated gut microbial alterations, highlighting potential mechanistic links and therapeutic targets.