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.