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Summary
This summary is machine-generated.

A core gut microbiome signature reliably predicts type 2 diabetes risk and future glucose increases. This microbiome risk score (MRS) was validated across multiple cohorts and linked to host metabolism and adiposity.

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Area of Science:

  • Microbiome research
  • Metabolic disease research
  • Human genetics

Background:

  • The gut microbiome plays a crucial role in host metabolism and disease development.
  • Identifying specific microbial features linked to type 2 diabetes (T2D) is essential for risk prediction and intervention.
  • Previous studies have suggested a link between gut microbiota and T2D, but a consistent core signature remains elusive.

Purpose of the Study:

  • To identify core gut microbial features associated with type 2 diabetes (T2D) risk.
  • To develop and validate a microbiome risk score (MRS) for T2D.
  • To explore demographic, adiposity, and dietary factors influencing the gut microbiome-T2D relationship.

Main Methods:

  • Utilized an interpretable machine learning framework on three Chinese cohorts (discovery and two validation) for cross-sectional analysis.
  • Constructed a microbiome risk score (MRS) based on identified microbial features.
  • Assessed prospective associations of MRS with glucose increment, host blood metabolites, and demographic/adiposity/dietary factors. Conducted fecal microbiota transplantation in germ-free mice.

Main Results:

  • A 14-feature MRS consistently associated with T2D risk across cohorts (RR per 1-unit MRS increase: 1.28, 1.23, 1.12).
  • MRS positively correlated with future glucose increment and various gut microbiota-derived blood metabolites.
  • Germ-free mouse studies confirmed the MRS-T2D relationship; body fat distribution emerged as a key modulator.

Conclusions:

  • A core gut microbiome signature is significantly associated with type 2 diabetes risk.
  • The developed microbiome risk score (MRS) demonstrates predictive value for T2D and future glucose changes.
  • Adiposity, particularly body fat distribution, influences the gut microbiome's role in T2D pathogenesis.