Comparative Analysis of Molecular Mechanisms Underlying DSS- and LPS-Induced Intestinal Inflammation in Mouse Organoids

Intestinal inflammation is a multifactorial pathology involving epithelial barrier disruption, immune dysregulation, and gut microbiota imbalance, with infectious enteritis (e.g., norovirus/Campylobacter jejuni-driven) being the most prevalent globally. Understanding its etiology is critical for targeted therapies. This study aimed to clarify mechanistic differences between dextran sulfate sodium (DSS) and lipopolysaccharide (LPS)-induced inflammation by establishing a mouse intestinal organoid(IO) model (retaining native mucosal features) treated with optimized DSS/LPS concentrations. Inflammatory responses were evaluated via barrier integrity (tight junction proteins), immune activation (cytokines), and transcriptomic/proteomic profiling. Results showed DSS induced inflammation through direct epithelial barrier disruption and NF-κB activation (mimicking chemical injury), upregulating repair-related genes. In contrast, LPS triggered Toll-like receptor 4(TLR4)-dependent signaling, driving tumor necrosis factor alpha(TNF-α)/Interleukin-6(IL-6) secretion (mimicking bacterial infection) with enriched pathogen recognition pathways. Conclusion: DSS models chemical barrier damage, while LPS models bacterial immune activation. These findings guide inducer selection for in vitro studies (DSS for barrier dysfunction, LPS for immune models), advancing standardization of organoid-based inflammation research.