Prominent mediatory role of gut microbiome in the effect of lifestyle on host metabolic phenotypes
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2025-12-31
Date Acceptance
2025-12-01
Citation
Gut Microbes, 2025, 17 (1)
ISSN
1949-0976
Publisher
Taylor & Francis Group
Journal / Book Title
Gut Microbes
Volume
17
Issue
1
Copyright Statement
© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41408736
Subjects
ADHERENCE
ASSOCIATIONS
DIETARY PATTERNS
DISEASE
DIVERSITY
Gastroenterology & Hepatology
Gut microbiome
INDEX
Life Sciences & Biomedicine
lifestyle
MARKERS
mediation
MEDITERRANEAN DIET
Microbiology
nutrition
QUALITY
RISK
Science & Technology
Publication Status
Published
Coverage Spatial
United States
Article Number
2599565
Date Publish Online
2025-12-17