| Summary: | Increasing evidence indicates that the gut microbiome (GM) plays an important role in dyslipidemia. To date, however, no in-depth characterization of the associations between GM with lipoproteins distributions (LPD) among adult individuals with diverse BMI has been conducted. To determine such associations, we studied blood-plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 Danes aged 19–89 years. Stratification of LPD segregated subjects into three clusters displaying recommended levels of lipoproteins and explained by age and body-mass-index. Higher levels of HDL2a and HDL2b were associated with a higher abundance of <i>Ruminococcaceae</i> and <i>Christensenellaceae</i>. Increasing levels of total cholesterol and LDL-1 and LDL-2 were positively associated with <i>Lachnospiraceae</i> and <i>Coriobacteriaceae</i>, and negatively with <i>Bacteroidaceae</i> and <i>Bifidobacteriaceae</i>. Metagenome-sequencing showed a higher abundance of biosynthesis of multiple B-vitamins and SCFA metabolism genes among healthier LPD profiles. Metagenomic-assembled genomes (MAGs) affiliated to <i>Eggerthellaceae</i> and <i>Clostridiales</i> were contributors of these genes and their relative abundance correlated positively with larger HDL subfractions. The study demonstrates that differences in composition and metabolic traits of the GM are associated with variations in LPD among the recruited subjects. These findings provide evidence for GM considerations in future research aiming to shed light on mechanisms of the GM–dyslipidemia axis.
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