Therapeutic effects of D-cycloserine in mouse models of IBD and CAC: Targeting NLRP3 inflammasome and intestinal barrier integrity

D-Cycloserine (DCS), a broad-spectrum antibiotic and NMDA receptor modulator, exhibits immunomodulatory effects beyond its known neurological and antimicrobial functions. This study investigated DCS's therapeutic potential in inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) using in vitro and in vivo models. In lipopolysaccharide (LPS)-stimulated NCM460 cells, DCS inhibited NLRP3 inflammasome activation and restored tight junction protein expression. In dextran sulfate sodium (DSS)-induced murine colitis, both preventive and therapeutic DCS regimens attenuated inflammation, reduced histopathological damage, and preserved intestinal barrier integrity. In azoxymethane (AOM)/DSS-induced CAC, DCS decreased tumor burden and reduced Ki-67+ cell proliferation without systemic toxicity. These findings position DCS as a promising dual-target candidate for IBD and CAC management through NLRP3-caspase-1-GSDMD pathway inhibition and epithelial barrier maintenance.