Insulin resistance modifies longitudinal multi-omics responses to habitual diet

Area of Science:

• Human physiology and metabolism
• Gut microbiome research
• Nutritional science and cardiovascular health

Background:

• The interplay between habitual diet, gut microbiome, and plasma metabolome in various insulin resistance states is not fully understood.
• Individual responses to diet can vary significantly, impacting metabolic health and disease risk.

Purpose of the Study:

• To investigate how habitual diet influences the gut microbiome and plasma metabolome in individuals with varying degrees of insulin resistance.
• To identify microbial and metabolic mediators of diet-omics associations.
• To assess the contribution of diet, metabolites, and microbial taxa to atherosclerotic cardiovascular disease risk.

Main Methods:

• Year-long multi-omics profiling (diet, metabolome, gut microbiome, clinical markers, inflammatory markers) in 71 adults.
• Gold-standard insulin suppression tests to assess insulin resistance.
• Machine learning to derive dietary patterns and analyze diet-omics associations stratified by insulin sensitivity.

Main Results:

• Insulin-sensitive individuals showed stronger diet-omics associations compared to insulin-resistant individuals, highlighting metabolic flexibility.
• The gut bacterium Parabacteroides was identified as a potential mediator linking refined carbohydrate intake to metabolic signatures.
• Diet, metabolites, microbial taxa, and immune markers independently contributed to 10-year atherosclerotic cardiovascular disease risk prediction.

Conclusions:

• Inter-individual variability in cardiometabolic risk is partly due to differences in molecular responsiveness to habitual diet.
• Findings support the role of metabolic flexibility and the gut microbiome in mediating dietary effects on health.
• Results have implications for precision nutrition and cardiovascular disease prevention strategies.