| Summary: | Cardiovascular disease (CVD) prevalence remains elevated globally. We have previously shown that a one-week lifestyle “immersion program” leads to clinical improvements and sustained improvements in quality of life in moderate to high atherosclerotic CVD (ASCVD) risk individuals. In a subsequent year of this similarly modeled immersion program, we again collected markers of cardiovascular health and, additionally, evaluated intestinal microbiome composition. ASCVD risk volunteers (<i>n</i> = 73) completed the one-week “immersion program” involving nutrition (100% plant-based foods), stress management education, and exercise. Anthropometric measurements and CVD risk factors were compared at baseline and post intervention. A subgroup (<i>n</i> = 22) provided stool, which we analyzed with 16S rRNA sequencing. We assessed abundance changes within-person, correlated the abundance shifts with clinical changes, and inferred functional pathways using PICRUSt. Reductions in blood pressure, total cholesterol, and triglycerides, were observed without reduction in weight. Significant increases in butyrate producers were detected, including <i>Lachnospiraceae</i> and <i>Oscillospirales</i>. Within-person, significant shifts in relative abundance (RA) occurred, e.g., increased <i>Lachnospiraceae</i> (+58.8% RA, <i>p</i> = 0.0002), <i>Ruminococcaceae</i> (+82.1%, <i>p</i> = 0.0003), <i>Faecalibacterium prausnitzii</i> (+54.5%, <i>p</i> = 0.002), and diversification and richness. Microbiota changes significantly correlated with body mass index (BMI), blood pressure (BP), cholesterol, high-sensitivity C-reactive protein (hsCRP), glucose, and trimethylamine N-oxide (TMAO) changes. Pairwise decreases were inferred in microbial genes corresponding to cancer, metabolic disease, and amino acid metabolism. This brief lifestyle-based intervention improved lipids and BP and enhanced known butyrate producers, without significant weight loss. These results demonstrate a promising non-pharmacological preventative strategy for improving cardiovascular health.
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