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Microbiome-Based Clustering Identifies Glycemic Control-Related Subtypes in Youth With Recent-Onset Type 1 Diabetes.

Huiling Tan1, Yu Ding1, Zhaohe Gu1

  • 1Department of Endocrinology and Metabolism The First Affiliated Hospital of USTC, University of Science and Technology of China Hefei Anhui China.

Medcomm
|April 3, 2026
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Summary

Microbiome analysis in children with type 1 diabetes revealed distinct gut bacteria profiles linked to glycemic control. Specific Bacteroides species and skatole may influence blood sugar regulation in youth.

Keywords:
endotypeglycemic controlgut microbiotamachine learningmulti‐omicstype 1 diabetes

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Area of Science:

  • Microbiome research
  • Metagenomics
  • Metabolomics
  • Pediatric endocrinology

Background:

  • Type 1 diabetes (T1D) in children shows varied glycemic control, with underlying biological mechanisms unclear.
  • Understanding heterogeneity in T1D is crucial for personalized treatment strategies.

Purpose of the Study:

  • To investigate endotype heterogeneity in recent-onset T1D using multi-omics data.
  • To identify molecular signatures and mechanisms associated with glycemic control variations in pediatric T1D.

Main Methods:

  • Unsupervised clustering of fecal metagenomic profiles in a discovery cohort (n=69).
  • Multi-omics data analysis including metabolomics.
  • Validation in an independent cohort and analysis in healthy children.

Main Results:

  • Two subgroups identified based on hemoglobin A1c (HbA1c) levels: High-HbA1c (enriched in Bacteroidota) and Low-HbA1c (enriched in Firmicutes and specific Bacteroides species).
  • Low-HbA1c group showed enrichment of tryptophan-derived metabolites, including skatole, correlated with Bacteroides signatures.
  • Bacteroides signatures accurately discriminated good versus poor glycemic control in validation (AUC=0.854).

Conclusions:

  • Microbiome-based clustering identified glycemic control-related subtypes in T1D youth.
  • Suggests a potential role for Bacteroides and skatole in regulating glycemic control.
  • Further mechanistic studies are needed to confirm these findings as a distinct pathophysiological endotype.