Longitudinal multi-omics of host-microbe dynamics in prediabetes

Area of Science:

• Metabolic health
• Immunology
• Microbiome research

Background:

• Type 2 diabetes (T2D) poses a growing health challenge, yet its early stages and biological underpinnings remain poorly understood.
• Investigating the transition from healthy states to prediabetes and T2D is crucial for early intervention strategies.

Purpose of the Study:

• To elucidate the earliest molecular and microbial changes associated with the progression towards T2D.
• To characterize individual variability in healthy and prediabetic states.
• To identify host-microbe interactions and immune responses in glucose dysregulation.

Main Methods:

• Longitudinal sampling from 106 healthy and prediabetic individuals over ~4 years.
• Deep multi-omics profiling: transcriptomes, metabolomes, proteomes, and cytokine analysis.
• Microbiome sequencing and analysis of host-microbe interactions.

Main Results:

• Healthy individuals exhibit distinct profiles with significant intra- and inter-personal variability.
• Respiratory viral infections and immunizations induce extensive host and microbial changes, with distinct immune responses.
• Insulin-resistant individuals show different responses to viral infections compared to insulin-sensitive individuals.
• Specific host-microbe interactions differ between insulin-resistant and insulin-sensitive states.
• Early molecular signatures, including IL-1RA and CRP, were identified preceding T2D onset in one individual.

Conclusions:

• The study provides novel insights into molecular and microbial pathways differentiating healthy, prediabetic, and T2D states.
• Identified host-microbe interactions and immune responses offer potential targets for T2D research.
• The comprehensive, open-access dataset will facilitate further investigation into T2D pathogenesis and early detection.