Sepsis, characterized by immune dysregulation and systemic inflammation, remains a major global health challenge. In critically ill patients, the gastrointestinal tract, liver, and pancreas are increasingly recognized as central players in disease progression and key sources of morbidity and mortality. The evolving understanding of sepsis and septic shock has increasingly shifted emphasis towards the critical role of gastrointestinal (GI) organ dysfunction—such as gut barrier failure, intestinal ischemia, liver injury, and pancreatic dysfunction—in driving systemic inflammation, bacterial/toxin translocation, and adverse outcomes. The concept of the gut as the "motor of multi-organ dysfunction syndrome" is particularly relevant here.

Despite advancements, numerous challenges persist in managing GI complications in sepsis. Gut dysbiosis, intestinal barrier dysfunction, and compromised splanchnic circulation are major contributors to systemic inflammation, bacterial translocation, and organ damage. Early diagnosis of specific GI involvement remains challenging due to overlapping symptoms and a lack of reliable, specific biomarkers of gut, liver, or pancreatic injury. Furthermore, standard treatments often fail to adequately address the complexities of splanchnic hypoperfusion, gut ischemia-reperfusion injury, and capillary leak that directly lead to GI organ damage and perpetuate multi-organ failure.

This Research Topic aims to address these critical gaps by exploring current challenges and advancing innovative solutions, specifically within the gastrointestinal system and its critical axis with the liver and pancreas. Recent advances offer promising avenues, including rapid diagnostics for gut barrier integrity, microbiome-targeted interventions (e.g., prebiotics, probiotics, fecal microbiota transplantation), targeted nutritional support, and immunomodulators focused on the gut-liver axis, though these are not yet widely implemented. The integration of GI organ-specific biomarkers (e.g., I-FABP, D-lactate, zonulin, liver function markers), artificial intelligence (AI)-driven protocols for early prediction, and personalized medicine approaches are key to improving patient outcomes by specifically focusing on the gut-liver-pancreas axis.

The scope of this collection invites contributions focusing on:

- Pathogenetic Mechanisms of GI Organ Dysfunction: Papers exploring the origins and mechanisms of sepsis or inflammation-driven gut barrier failure, intestinal ischemia, liver injury, pancreatic dysfunction, and the role of bacterial/toxin translocation from the gut in the critically ill context.

- Emerging Fields: The Gut Microbiome, Virome, and Fungi: The role of gut dysbiosis, gut-derived viral and fungal involvement in sepsis, and their identification through novel biomarkers, as well as the impact of therapeutic interventions on the GI microbiome.

- Advanced Diagnostics for GI Injury and Infection: Utility and pitfalls of molecular techniques such as Multiplex PCR and Next-Generation Sequencing (NGS) for early pathogen detection from GI samples (e.g., peritoneal fluid, gut biopsies) or systemic infections with a suspected GI origin, as well as biomarkers for intestinal permeability, splanchnic hypoperfusion, and liver/pancreatic damage.

- Host Response & Signaling in GI Organs: Investigations into key signaling pathways and host responses driving sepsis outcomes, specifically focusing on stress-signaling pathways, mitochondrial dysfunction, and epithelial cell damage within the intestinal epithelium, hepatocytes, and pancreatic cells.

- Therapeutic Strategies Targeting the GI System: Interventions aimed at restoring gut barrier function, modulating the microbiome, improving splanchnic perfusion, or providing specific nutritional support in critically ill septic patients.

By identifying gaps in current knowledge, this collection seeks to foster research that guides personalized treatment strategies, discovers novel biomarkers of GI injury, and evaluates emerging therapies focused on preserving and restoring gastrointestinal, hepatic, and pancreatic health during sepsis. The ultimate goal is to refine clinical protocols and enhance patient care for sepsis-related complications, underscoring the urgent need for continued research in this critical area from a gastroenterological perspective.

Are you interested in contributing a manuscript to this Research Topic?

The Gut, Liver, and Pancreas in Sepsis and Sterile Inflammation in the Critically Ill