Narrative review offers a theoretical framework for personalized management of acute upper gastrointestinal bleeding in patients

Acute upper gastrointestinal bleeding (UGIB) is a critical emergency commonly encountered in gastroenterology. Its pathogenesis is complex and involves diverse etiologies. Emerging evidence indicates that pyroptosis, dysregulated immune-inflammatory responses, and gut microbiome imbalance are pivotal mechanisms driving gastric mucosal injury and hemorrhage. This review systematically synthesizes the risk factors, pathophysiological mechanisms, risk prediction models, and therapeutic strategies for UGIB, with particular emphasis on the intricate interplay among pyroptosis, immunity, and the microbiome and on their value as potential therapeutic targets. We first summarize the common etiologies and risk factors of UGIB, including pharmacological agents, infections, advanced age, comorbidities, and genetic predispositions. We then delineate the pathogenic role of pyroptosis in gastric mucosal injury, with particular focus on activation of the GKN2-NLRP3 axis. Next, we discuss the utility of systemic inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in UGIB risk stratification, together with the mechanisms by which gut microbiome dysbiosis compromises mucosal barrier integrity and amplifies inflammatory responses through microbial metabolites and pathogen translocation. The core section provides an in-depth analysis of the reciprocal, self-amplifying network linking pyroptosis, immune activation, and microbiome perturbation, thereby elucidating the basis for the frequent co-occurrence of systemic inflammation and microbial dysbiosis in UGIB. Finally, we critically evaluate established risk-scoring systems (Glasgow-Blatchford Score, Rockall score, and AIMS65) and emerging biomarkers. Overall, this review assesses emerging therapeutic strategies, including pyroptosis inhibitors and microbiome-modulating interventions, and provides a theoretical framework for personalized management of UGIB.