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Prominent mediatory role of gut microbiome in the effect of lifestyle on host metabolic phenotypes.
Gut Microbes 17:2599565 (2025)
Lifestyle factors influence both gut microbiome composition and host metabolism, yet their combined and mediating effects on host phenotypes remain poorly characterized in cardiometabolic populations. In 1,643 participants from the MetaCardis study, we developed a composite lifestyle score (QASD: dietary quality, physical activity, smoking, and diet diversity) that outperformed individual lifestyle variables in explaining microbial gene richness and exhibited a significant impact on the gut microbiome composition. While bidirectional pathways linking the QASD score, host phenotypes, and microbiome composition were assessed, causal inference-based mediation analyses indicated stronger effects when the microbiome was modeled as the mediator variable, particularly in relation to the insulin resistance-associated profile. Microbiome gene richness emerged as a key mediator explaining 27.8% of QASD score's effect on the insulin resistance marker (HOMA-IR), while no significant mediation was observed on BMI. Extended mediation analyses on microbial species and serum metabolomics deconfounded for drug use and clinical profiles identified 47 mediations where microbial taxa mediated more than 20% of the effect of the QASD score on serum metabolites associated with insulin resistance. Notably, several Faecalibacterium lineages enriched in individuals with high QASD score played a significant mediatory role in increasing the serum biomarkers of microbiome diversity (as cinnamoylglycine or 3-phenylpropionate). Conversely, elevated levels of secondary bile acids in individuals with low QASD scores were strongly mediated by high levels of Clostridium bolteae. These findings highlight distinct and clinically relevant microbiome pathways linking lifestyle behaviors to cardiometabolic risks.One sentence summary:The gut microbiome mediates the impact of diet quality and diversity, physical activity and smoking status - combined in a composite lifestyle score - on cardiometabolic phenotypes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Gut Microbiome ; Lifestyle ; Mediation ; Nutrition; Dietary Patterns; Mediterranean Diet; Risk; Disease; Quality; Markers; Index; Associations; Diversity; Adherence
ISSN (print) / ISBN
1949-0976
e-ISSN
1949-0984
Journal
Gut Microbes
Quellenangaben
Volume: 17,
Issue: 1,
Article Number: 2599565
Publisher
Landes Bioscience
Publishing Place
530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants
Isite ULNE
Medical Research Council Centre for Neurodevelopmental Disorders
Agence Nationale de la Recherche
European Metropolis of Lille
EIC-pathfinder
National Center for Diabetes Precision Medicine
NIHR Imperial Biomedical Research Centre
European Commission
Hauts-de-France Regional Council
Guts UK
Deutsche Forschungsgemeinschaft
Deutsches Zentrum fr Herz-Kreislaufforschung
Fondation Leducq
Medical Research Council
Diabetes UK
European Commision
European Union (FEDER)
Wellcome Trust
European Central Bank
Medical Research Council Centre for Neurodevelopmental Disorders
Agence Nationale de la Recherche
European Metropolis of Lille
EIC-pathfinder
National Center for Diabetes Precision Medicine
NIHR Imperial Biomedical Research Centre
European Commission
Hauts-de-France Regional Council
Guts UK
Deutsche Forschungsgemeinschaft
Deutsches Zentrum fr Herz-Kreislaufforschung
Fondation Leducq
Medical Research Council
Diabetes UK
European Commision
European Union (FEDER)
Wellcome Trust
European Central Bank