Propionate alleviates ulcerative colitis by modulating the PI3K/AKT signaling pathway and suppressing NLRP3 inflammasome activation.

Background: Ulcerative colitis (UC) poses a significant health challenge characterized by recurrent inflammation of the intestinal tract, yet effective treatment options remain elusive. While previous studies have hinted at the potential of propionate, a short-chain fatty acid (SCFA), in mitigating colitis, the underlying mechanism remains unclear. Purpose: This study aims to elucidate the therapeutic effects of propionate in dextran sulfate sodium (DSS)-induced colitis and explore its regulatory influence on the NLRP3 inflammasome and associated signaling pathways. Methods: In vivo, we employe two kinds of DSS-induced colitis model to examine propionate's impact on the NLRP3 inflammasome. Additionally, in vitro investigations were conducted using the RAW264.7 cell line. Results: Our findings present compelling evidence that propionate effectively ameliorates DSS-induced colitis by impeding NLRP3 inflammasome activation. This intervention leds to a reduction in pro-inflammatory factors, restoration of the epithelial barrier, and downregulation of the PI3K/AKT signaling pathway. Notably, these effects are mediated through the activation of its receptor GPR43. Conclusions: This pioneering study establishes propionate as a potent agent in alleviating UC by suppressing NLRP3 inflammasome activation. The propionate-NLRP3 axis emerges as a promising therapeutic target for inflammatory diseases, opening new avenues for treatment strategies in UC.