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

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.