From Inflammasomes to Pyroptosis: Molecular Mechanisms in Chronic Intestinal Diseases — Opportunity or Challenge?

Jintao Fang,1,* Weihan Zhu,1,* Dian Yu,1 Lujian Zhu,2 Haorui Zha,1 Jingyi Tang,3 Yujia Li,1 Xiaxin Zhu,1 Ting Zhao,1 Wei Zhang1,4 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 2Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, 321000, People’s Republic of China; 3Lanxi Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang, 321100, People’s Republic of China; 4Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China, Email [email protected]: Pyroptosis is a unique form of programmed cell death characterized by intense inflammation. It involves the activation of Gasdermin proteins, which form membrane pores, leading to rapid cell rupture and the release of inflammatory molecules. Unlike other types of cell death, pyroptosis has distinct activation mechanisms and plays a complex role in chronic intestinal diseases, including inflammatory bowel disease, intestinal fibrosis, chronic infectious enteritis, and colorectal cancer. This review comprehensively examines how pyroptosis influences disease development and progression while exploring the therapeutic potential of targeting pyroptosis-related pathways. Moreover, the complex interplay between gut microbiota and pyroptosis is summarized, highlighting its critical role in the pathogenesis of chronic intestinal disorders. A deeper understanding of pyroptosis-related mechanisms in these diseases may provide valuable insights for future research and contribute to the development of innovative therapeutic strategies in gastroenterology.Keywords: pyroptosis, chronic intestinal diseases, inflammasomes, gasdermin proteins, cell death