# Microbial metabolites associated with healthy lifestyles in relation to metabolic syndrome and vascular health: a cross-sectional study

## TL;DR

Healthy lifestyle habits are linked to specific gut bacteria and metabolites that may lower the risk of metabolic syndrome and improve vascular health.

## Contribution

The study identifies specific gut microbes and metabolites that mediate the relationship between healthy lifestyles and metabolic/vascular health.

## Key findings

- Higher Healthy Lifestyle Score correlates with increased abundance of Alistipes putredinis, Odoribacter splanchnicus, and Roseburia hominis.
- Cinnamoylglycine and betaine, from homolactic fermentation, are potential mediators of vascular and metabolic benefits.
- Microbial metabolic pathways are independently linked to both lifestyle score and metabolic syndrome risk.

## Abstract

Lifestyle behaviors influence the risk of metabolic syndrome (MetS) and affect vascular health. However, the interactions between gut microbiota and lifestyle behaviors in relation to MetS, as well as the specific microbial taxa and metabolites involved, remain unclear. Here, we aimed to investigate the associations among healthy lifestyle behaviors, gut microbiota, and MetS and to explore the potential mediating roles of microbially derived metabolites in these associations. A total of 1,342 participants with complete assessments of the Healthy Lifestyle Score (HLS), MetS, and vascular health were enrolled. Fecal samples were collected and subjected to metagenomic sequencing. Host genetic data were obtained using a high-density genotyping array, and plasma metabolites were quantified by liquid chromatography–mass spectrometry. Using generalized linear models, we found that increased abundances of Alistipes putredinis, Odoribacter splanchnicus, and Roseburia hominis were associated with higher HLS and a reduced risk of MetS. Eleven microbial metabolic pathways were independently correlated with both HLS and MetS. Furthermore, increased plasma levels of cinnamoylglycine and betaine, driven by enhanced microbial capacity for homolactic fermentation, were identified as potential microbial effectors associated with MetS and vascular health. These findings indicate that the association between HLS and MetS may involve modulation of the gut microbiota and their metabolites and highlight the potential to enhance the beneficial effects of healthy behaviors on MetS and vascular health through microbiota-modifying interventions.

Metabolic syndrome raises the risk of heart disease and diabetes, yet practical levers to prevent it remain limited. We show that everyday healthy habits align with a gut microbial “signature” linked to better vascular health and lower metabolic risk. Using metagenomics, metabolomics, and genetic causal analyses, we identify specific bacteria (Alistipes putredinis, Odoribacter splanchnicus, and Roseburia hominis) and microbially produced molecules—especially cinnamoylglycine and betaine from enhanced homolactic fermentation—that may mediate these benefits. These findings connect lifestyle, the gut microbiome, and blood metabolites in a single framework, suggesting actionable biomarkers to monitor risk and potential microbiota-targeted strategies (diet and pre/probiotics) to improve cardiometabolic health. By highlighting concrete microbial pathways and metabolites, our work advances the path toward precision prevention and low-cost interventions for metabolic syndrome and vascular disease.