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Purpose <p>Diabetic ketoacidosis (DKA) stands as the most common acute hyperglycaemic complication in children with type 1 diabetes (T1D) and remains associated with considerable morbidity and mortality. Although gut dysbiosis has been reported in newly diagnosed T1D, the gut microbiota and microbial metabolites during DKA onset remain poorly characterized.</p> Methods <p>Shotgun metagenomic sequencing was performed on fecal samples from 96 newly diagnosed T1D children, including 32 presenting with DKA upon admission. Short-chain fatty acids (SCFAs) were quantified using gas chromatography/mass spectrometry (GC/MS). Comparative and correlation analyses were conducted to explore differences in gut microbial composition, SCFA levels, and their association with clinical indicators of DKA severity.</p> Results <p>Children with DKA exhibited distinct gut microbial compositions, with marked β-diversity separation from non-DKA individuals. The DKA group was characterized by an enrichment of potential pathogens and a significant depletion of SCFA-producing genera, including <i>Anaerobutyricum</i>, <i>Dialister</i>, <i>Ruminococcus</i>, <i>Roseburia</i>, <i>Dorea</i>, and <i>Butyricicoccus</i>. Correspondingly, fecal SCFA levels were significantly reduced in the DKA group. Moreover, SCFAs and their producing bacteria were strongly correlated with clinical indices of DKA severity. Mediation analysis suggested that reductions in SCFAs, particularly propionic acid and butyric acid, were associated with metabolic alterations linking SCFA-producing bacteria to DKA.</p> Conclusion <p>This study provides a comprehensive characterization of gut microbiota and SCFA alterations in T1D children at DKA onset. The depletion of SCFA-producing bacteria and their metabolites reflects metabolic disturbances associated with DKA, and highlights SCFAs and their producers as candidate metabolic features warranting further validation as biomarkers and therapeutic targets.</p>

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Gut microbiota dysbiosis and short-chain fatty acid alterations in pediatric new-onset type 1 diabetes with ketoacidosis

  • 期刊论文

  • 发表日期：

    2026年6月25日

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  • Yaru Liu,
  • Hu Lin,
  • Mingqiang Zhu,
  • Xuefeng Chen,
  • Zhu Yu,
  • Dandan Peng,
  • Guanping Dong,
  • Yan Ni,
  • Junfen Fu

摘要

Purpose

Diabetic ketoacidosis (DKA) stands as the most common acute hyperglycaemic complication in children with type 1 diabetes (T1D) and remains associated with considerable morbidity and mortality. Although gut dysbiosis has been reported in newly diagnosed T1D, the gut microbiota and microbial metabolites during DKA onset remain poorly characterized.

Methods

Shotgun metagenomic sequencing was performed on fecal samples from 96 newly diagnosed T1D children, including 32 presenting with DKA upon admission. Short-chain fatty acids (SCFAs) were quantified using gas chromatography/mass spectrometry (GC/MS). Comparative and correlation analyses were conducted to explore differences in gut microbial composition, SCFA levels, and their association with clinical indicators of DKA severity.

Results

Children with DKA exhibited distinct gut microbial compositions, with marked β-diversity separation from non-DKA individuals. The DKA group was characterized by an enrichment of potential pathogens and a significant depletion of SCFA-producing genera, including Anaerobutyricum, Dialister, Ruminococcus, Roseburia, Dorea, and Butyricicoccus. Correspondingly, fecal SCFA levels were significantly reduced in the DKA group. Moreover, SCFAs and their producing bacteria were strongly correlated with clinical indices of DKA severity. Mediation analysis suggested that reductions in SCFAs, particularly propionic acid and butyric acid, were associated with metabolic alterations linking SCFA-producing bacteria to DKA.

Conclusion

This study provides a comprehensive characterization of gut microbiota and SCFA alterations in T1D children at DKA onset. The depletion of SCFA-producing bacteria and their metabolites reflects metabolic disturbances associated with DKA, and highlights SCFAs and their producers as candidate metabolic features warranting further validation as biomarkers and therapeutic targets.