Targeting P2X7 receptor/NLRP1 inflammasome axis and gut dysbiosis: A mechanistic review of pyroptosis in metabolic inflammation

Chronic NLRP1 hyperactivation fosters a self-perpetuating "vicious cycle" of tissue damage, insulin resistance, and β-cell attrition, leading to macrovascular and microvascular complications. To disrupt this cascade, a multi-faceted therapeutic approach is required. Restoring the intestinal barrier through probiotics and short-chain fatty acids (SCFAs) can limit the circulation of inflammatory primers. Concurrently, targeting the P2X7R/NLRP1 axis with specific antagonists and inflammasome inhibitors provides a pragmatic strategy to reduce systemic inflammation. This review elucidates the complex interplay between these pathways and proposes a combination therapy to mitigate the chronic inflammatory burden of obesity and T2D.