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Aim: To investigate the impact of type 1 diabetes mellitus(T1DM)on the bactericidal function of intestinal Paneth cells.Methods: T1DM mice were induced by intraperitoneal injection of streptozocin(STZ).The mice were divided into three groups: control mice(n=10),STZ-induced diabetic mice(n=10),and insulin-treated diabetic mice(n=10).Numbers of Paneth cells and their expression of related antimicrobial peptides were analyzed.The mucosal bactericidal assay and the analysis of intestinal microbiota were respectively conducted to evaluate the Paneth cell bactericidal function.The primary mouse small intestinal crypt culture was used to analyze the effect of insulin and glucose on the expression of related antimicrobial peptides of Paneth cells.Results: The expression of Paneth cell-derived antimicrobial peptides was significantly decreased in the T1DM mice although the number of Paneth cells in the distal intestine was slightly increased.The bactericidal activity of Paneth cells was reduced and exogenous bacteria were easier to survive in the small bowel of the T1DM mice.Moreover,the bacterial loads were increased and there was an alteration in the composition of the intestinal microflora.Insulin treatment restored the expression of antimicrobial peptides and normalized the microbiota in the gut of T1DM mice.Subsequently,in vitro culture assay demonstrated that insulin rather than glucose was essential for the optimal expression of Paneth cell-derived antimicrobial peptides.Conclusions: The deficiency of insulin could result in the impairment of the bactericidal function of Paneth cells in the small intestine,leading to an alteration in the intestinal flora.