Gut Microbiota and Molecular Modulators of Pyroptosis: Mechanisms and Therapeutic Strategies in Gastrointestinal Cancer and Inflammatory Bowel Disease

Pyroptosis, a form of inflammatory programmed cell death mediated by the gasdermin protein family, plays a pivotal and context-dependent role in gastrointestinal pathophysiology. In gastrointestinal cancers, pyroptosis can act as a tumor-suppressive mechanism while paradoxically fostering an inflammatory microenvironment that promotes tumor progression. In inflammatory bowel disease (IBD), dysregulated pyroptosis of intestinal epithelial and immune cells drives chronic mucosal inflammation and barrier dysfunction.The gut microbiota is increasingly recognized as a central regulator of pyroptotic signaling in the gut, through microbial metabolites (e.g., short-chain fatty acids, secondary bile acids), pathogen-associated molecular patterns, and host-microbiota crosstalk. In parallel, a broad range of molecular modulators — including natural compounds, synthetic small-molecule inhibitors, and biologics — are being explored to pharmacologically target pyroptosis-related pathways (NLRP3/NLRP1/AIM2 inflammasomes, GSDMD/GSDME cleavage). This Research Topic aims to bring together current advances at the intersection of gut microbiota, pyroptosis regulation, and therapeutic development for gastrointestinal cancer and IBD.We welcome Original Research, Review, Mini Review, and Systematic Review articles addressing (but not limited to):Gut microbiota, microbial metabolites, and natural compounds as regulators of pyroptosis in gastrointestinal cancer and IBDMolecular mechanisms of pyroptosis (inflammasome activation, gasdermin cleavage) in gut pathologyPharmacological agents — natural compounds, synthetic small molecules, biologics — targeting pyroptosis-related pathwaysHost-microbiota-immune crosstalk in pyroptosis-driven gastrointestinal diseasePreclinical and clinical evidence for pyroptosis-targeted therapeutic strategiesBiomarkers of pyroptosis activity for diagnosis, prognosis, or treatment response Topic editors: Wenbin Gong, Konrad Dr Aden Source: https://www.frontiersin.org/research-topics/84831/gut-microbiota-and-molecular-modulators-of-pyroptosis-mechanisms-and-therapeutic-strategies-in-gastrointestinal-cancer-and-inflammatory-bowel-disease