Researchers at the Samsung Advanced Institute for Health Sciences and Technology at Sungkyunkwan University in Seoul have identified specific gut bacteria that may contribute to the development of dyslipidemia, a precursor to cardiovascular disease. The research, published in Microbiology Spectrum, found distinct differences in gut microbial communities between individuals with abnormal lipid levels and those with healthy profiles and linked particular bacterial taxa to metabolic pathways that influence lipid metabolism.
“Dyslipidemia is common and often clinically silent,” said study leader Han-Na Kim, PhD, a geneticist at Samsung Advanced Institute for Health Sciences and Technology. “Studying microbial alterations at this stage provides insight into biological shifts that may occur before clinical cardiovascular disease manifests.”
For this research, the investigators analyzed fecal and blood samples from 1,384 participants, including 895 with dyslipidemia. Using shotgun metagenomic sequencing, the researchers found that in people with dyslipidemia a bacterial species that has been associated with inflammation and metabolic disturbances, Bacteroides caccae, was enriched. Study participants with with healthy lipid levels had higher prevalence of short-chain fatty acid (SCFA)-producing bacteria, including Coprococcus eutactus, Coprococcus catus, and Blautia obeum, which previous studies have linked to anti-inflammatory effects and regulation of lipid metabolism.
“Dyslipidemia appears to be associated with a reduction in bacteria linked to metabolic stability and an enrichment of taxa that may reflect altered lipid and inflammatory states,” the researchers wrote.
Beyond simply studying the bacterial composition of the gut, the team also examined microbial metabolic pathways. Dyslipidemia study subjects showed enrichment of the dTDP-beta-D-fucofuranose biosynthesis pathway, linked to bacterial pathogenicity and inflammation. At the same time, glycogen and peptidoglycan biosynthesis pathways were reduced, which the researcher said could affect energy storage and immune function. Predicted metabolite analyses suggested lower levels of pseudouridine in individuals with dyslipidemia, highlighting coordinated shifts in microbial function.
The Samsung team also explored the gut the collection of antimicrobial resistance genes, called the resistome. A marginal increase in the tetracycline-resistance gene tetQ was observed in dyslipidemia cases, though the effect size was modest and statistical significance diminished after adjusting for host factors.
The study builds on prior research that has indicated links between gut microbiota and lipid metabolism. Observational and Mendelian Randomization studies have associated genera such as Prevotella, Bacteroides, Akkermansia, and Escherichia/Shigella with blood lipid levels, hinting at the potential causes of dyslipidemia. However, many prior research efforts were conducted using lower resolution sequencing technologies that only provided genus-level resolution. By employing shotgun metagenomic sequencing, this new study was able to characterize bacterial species, metabolic pathways, and predicted metabolites in much greater detail.
To identify the associations discovered, the researcher adjusted for host variables including age, sex, BMI, blood glucose, and blood pressure, which revealed bacterial species-level patterns that were not apparent in unadjusted data analyses. Exploratory stratified analyses demonstrated that microbial differences were more pronounced in individuals with higher metabolic risk profiles.
The researchers will now conduct longitudinal and experimental studies to validate these findings and attempt to determine causality. Kim noted that any new research efforts will focus on the broader microbial ecosystem of the gut, rather than on individual bacteria species. “Future translational efforts should focus on restoring functional balance at the community level, rather than targeting one organism in isolation,” he said.
