Monday, March 30, 2026

Escherichia-Shigella expansion, reduced diversity distinguish T3cDM gut microbiome from T1DM

Key Takeaway
Consider that gut microbiome alterations in T3cDM, marked by Escherichia-Shigella expansion, are linked to exocrine pancreatic insufficiency rather than systemic metabolic disturbance.

This study investigated gut microbiome alterations in pancreatogenic diabetes (type 3c diabetes, T3cDM) to determine if changes reflect systemic metabolic disturbances or primarily arise from exocrine pancreatic insufficiency (EPI). The research profiled the gut microbiome of 48 outpatients, including individuals with T3cDM, type 1 diabetes (T1DM), and healthy controls. Genus-level 16S rRNA data were analyzed using cross-validated LASSO logistic regression and patient-specific community metabolic models. Results showed T3cDM had reduced α-diversity and distinct β-diversity compared with both T1DM and healthy controls. Key compositional shifts in T3cDM included enrichment of the families Enterobacteriaceae (notably the genus Escherichia–Shigella) and Streptococcaceae. The LASSO logistic regression model identified specific bacterial genera as predictors, successfully discriminating T3cDM from T1DM with an area under the curve (AUC) of 0.867 and an accuracy of 0.818. The model highlighted Blautia, Escherichia–Shigella, Streptococcus, Clostridium, and Faecalibacterium as key predictors. Metabolic modeling indicated elevated growth of Escherichia–Shigella in T3cDM and revealed disease-specific metabolite fluxes. The study concludes that the observed gut microbial shifts in T3cDM predominantly reflect exocrine pancreatic insufficiency rather than the systemic metabolic disturbances characteristic of T1DM. This underscores the central role of exocrine pancreatic dysfunction in shaping the gut microbiome and its metabolic activity.

View Original Abstract ↓
Emerging evidence supports a bidirectional gut–pancreas axis in which microbial dysbiosis, barrier dysfunction, and altered metabolite fluxes contribute to pancreatogenic diabetes (T3cDM). Whether gut microbial changes reflect systemic metabolic disturbances or primarily arise from exocrine pancreatic insufficiency (EPI) remains unclear. We profiled the gut microbiome of 48 outpatients with T3cDM, type 1 diabetes (T1DM), and healthy controls. Genus-level 16S rRNA data were analyzed using cross-validated LASSO logistic regression and patient-specific community metabolic models. T3cDM showed reduced α-diversity and distinct β-diversity compared with T1DM and controls. Key compositional shifts included enrichment of Enterobacteriaceae (notably Escherichia–Shigella) and Streptococcaceae in T3cDM. LASSO models discriminated T3cDM from T1DM (AUC 0.867; accuracy 0.818), highlighting Blautia, Escherichia–Shigella, Streptococcus, Clostridium, and Faecalibacterium as predictors. Metabolic modelling indicated elevated Escherichia–Shigella growth in T3cDM and disease-specific metabolite fluxes. Gut microbial shifts in T3cDM predominantly reflect EPI rather than systemic metabolic disturbances characteristic of T1DM, underscoring the central role of exocrine pancreatic dysfunction in shaping the gut microbiome and its metabolic activity.