Inulin Protects Caco-2 Cells Against Lipopolysaccharide-Induced Epithelial Barrier Dysfunction

Abstract

Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, triggers inflammatory responses in intestinal epithelial cells. This activation leads to the production of pro-inflammatory cytokines which disrupt cellular homeostasis. LPS also impairs the integrity of the intestinal epithelial barrier by downregulating tight junction proteins, resulting in increased intestinal permeability. This compromised barrier function can allow further translocation of luminal antigens, perpetuating inflammation and contributing to gut-related disorders such as inflammatory bowel disease (IBD) and metabolic endotoxemia. This study investigated the therapeutic effects of inulin, a prebiotic dietary fiber, in attenuating LPS-induced intestinal epithelial barrier dysfunction. Caco-2 cells were treated with 100 ng/mL of LPS for 12 h, resulting in increased gene expression of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-18) and a significant downregulation of tight junction proteins claudin-1 and claudin-2, while occludin gene expression remained unaffected. Pretreatment with 2% inulin for 24 h before LPS exposure prevented the downregulation of claudin-1 and claudin-2 and significantly upregulated occludin gene expression. These molecular findings were supported by functional assays using transwell systems. LPS treatment increased paracellular permeability of the Caco-2 monolayer, indicating barrier dysfunction, while inulin pretreatment mitigated this effect. These results demonstrate that inulin can modulate tight junction protein expression and maintain gut barrier integrity under inflammatory conditions.