Feed

Interactions between the gut microbiota and inflammatory pathways contribute to intestinal alterations associated with type 1 diabetes mellitus (T1DM). Annexin A1 (AnxA1) is a pro-resolving protein implicated in epithelial homeostasis and inflammasome regulation. This study investigated the role of AnxA1 in intestinal epithelial alterations and NLRP3 inflammasome-associated responses during T1DM. Wild-type (WT) and AnxA1-deficient mice were assigned to control or diabetic groups following streptozotocin-induced diabetes. Intestinal tissues were analyzed using histological, immunohistochemical, molecular, and multiplex cytokine/growth factor approaches. Diabetes induction reduced goblet cell density in both genotypes, whereas AnxA1 deficiency was associated with increased epithelial thickness and reduced E-cadherin expression. ZO-1 levels were decreased in both diabetic groups compared with controls. Diabetic WT mice exhibited increased inflammatory mediator production, whereas AnxA1-deficient mice displayed attenuated classical inflammatory responses but increased expression of NLRP3 inflammasome-associated proteins, including NLRP3, ASC, and cleaved caspase-1. Epidermal growth factor levels were reduced only in AnxA1-deficient diabetic mice. Collectively, these findings indicate that AnxA1 contributes to the regulation of intestinal epithelial homeostasis and inflammatory responses during diabetes. Furthermore, AnxA1 deficiency was associated with increased expression of NLRP3, inflammasome-related components, suggesting a potential role for AnxA1 in modulating inflammasome-associated pathways in the diabetic intestine. These findings highlight AnxA1 as a potential therapeutic target for intestinal complications associated with T1DM.