Sodium Butyrate Regulates Gasdermin B Exerted Protection Effect on the MTX‐Induced NCM460 and Hum Cells

Abstract

AbstractInflammatory bowel disease (IBD) is a complex disorder with unclear etiology, and the impact of short‐chain fatty acids (SCFAs) on its pathogenesis is not well‐studied. This research explores the potential protective effects of sodium butyrate (NaB) in inflammatory bowel disease (IBD) through the Gasdermin B (GSDMB) non‐pyroptotic pathway. Fecal SCFA levels and GSDMB‐related proteins of IBD patients are analyzed. NCM460 and HUM cells are treated with methotrexate (MTX) for 24 hours. NaB is applied at concentrations of 1, 5, and 10 mm mL−1 to cells. It is found that a decrease in SCFAs content, zonula occludens‐1 (ZO‐1), and Occludin expression, along with an increase in GSDMB, focal adhesion kinase (FAK), and extracellular singal‐regulated kinase (ERK) in IBD patients is observed. NaB, at medium and high concentrations, promotes cell viability and migration and increased GSDMB expression. The low concentration of NaB has a significant protective effect on IBD‐affected cells, activating the GSDMB non‐pyroptotic pathway. This protection diminishes after the GSDMB knockdown. The study reveals that NaB may play a crucial role in protecting intestinal epithelial integrity in IBD through the GSDMB non‐pyroptotic pathway. These findings underline the potential of targeting this pathway for therapeutic strategies, highlighting the importance of SCFAs in understanding and treating IBD.