The inflammatory bowel disease and gut microbiome are restored by employing metformin-loaded alginate-shelled microcapsules

Abstract

Inflammatory bowel disease (IBD) is a chronic or recurrent inflammatory disorder affecting various parts of the gastrointestinal tract. Metformin, a widely prescribed hypoglycemic drug for type 2 diabetes, has shown potential in reducing IBD risk. However, its oral administration faces significant challenges due to the harsh gastrointestinal environment, requiring higher or more frequent doses to achieve therapeutic effects, which increases the risk of side effects. To address this, we developed alginate-shelled hydrogel microcapsules with a thin oil layer for targeted intestinal delivery of metformin. The oil layer protects metformin from gastric acid and ensures its release specifically in the intestines. In a dextran sulfate sodium-induced colitis mouse model, metformin-loaded hydrogel microcapsules (MHM) significantly reduced disease activity, intestinal epithelial damage, and macrophage infiltration linked to pro-inflammatory cytokine factors. Additionally, MHM improved dysbiosis of specific bacterial genera, including Bacteroides vulgatus, Lactobacillus (L.) gasseri, L. reuteri, and L. intestinalis, optimizing the abundance and composition of microorganisms. These findings indicate that encapsulating metformin within alginate shelled-microcapsules with a thin oil layer presents a potential delivery system for IBD treatment.

Keywords: Alginate-shelled hydrogel microcapsule; Colonic inflammation; Gut microbiota; Metformin; Oral delivery.