Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes.

Summary

In two Swedish cohorts, >500 metabolites associated with impaired glucose control were identified, about one-third linked to altered gut microbiota. Microbiome-associated metabolites were modulated by short-term lifestyle changes (diet/exercise), highlighting a modifiable microbiome–metabolome axis influencing glycemic homeostasis.

Key Findings

• Identified >500 circulating metabolites associated with impaired glucose control in two cohorts (n=1,167).
• Approximately one-third of these metabolites were linked to gut microbiome alterations.
• Short-term lifestyle changes modulated microbiome-associated metabolites in a lifestyle-specific manner.

Clinical Implications

Supports integrating microbiome–metabolome profiling to stratify T2D risk and tailor diet/exercise interventions, potentially improving adherence and glycemic outcomes via personalized targets.

Limitations

• Observational design limits causal inference despite robust associations
• Generalizability beyond European ancestry cohorts requires validation

Future Directions

Interventional trials targeting microbiome–metabolome nodes; mechanistic studies of key microbe–metabolite pairs (e.g., hippurate pathways) and precision lifestyle prescriptions.