Beyond the Pancreas: The Gut Microbiota in Acute Pancreatitis - From Mechanisms to Therapeutic Perspectives.

Abstract

Acute pancreatitis is a heterogeneous inflammatory disease in which severe forms are frequently complicated by intestinal barrier failure, dysbiosis, bacterial translocation, infected necrosis, systemic inflammation, and organ dysfunction. Growing clinical and experimental evidence suggests that the gut microbiota may contribute to disease progression and represents a potential, although incompletely validated, therapeutic target. Importantly, acute pancreatitis-associated dysbiosis involves not only taxonomic shifts but also functional metabolic reprogramming, including reduced short-chain fatty acid production, altered microbial bile acid transformation, and disturbances in amino acid and lipid metabolism that may contribute to barrier dysfunction and systemic inflammation. This review synthesizes current evidence on microbiota-oriented strategies in acute pancreatitis, with emphasis on clinical applicability, mechanistic rationale, and safety. This narrative review integrates clinical guidelines, randomized trials, meta-analyses, cohort studies, metagenomic and metabolomic investigations, and experimental studies published mainly between 2002 and 2026. Among clinically supported strategies, early oral or enteral nutrition has the strongest evidence base and may help preserve mucosal integrity while limiting the ecological consequences of fasting and critical illness. Antimicrobial stewardship is also fundamental, because unnecessary antibiotic exposure may aggravate dysbiosis, impair colonization resistance, and promote resistant organisms. Selective digestive decontamination has historical clinical evidence but is not established for routine contemporary practice. Prebiotics, dietary fibers, postbiotics, and metabolite-oriented approaches are mechanistically promising, but clinical evidence remains limited. GV-971 is currently supported predominantly by preclinical experimental data. Probiotics and synbiotics require caution, particularly in predicted severe disease, because clinical benefits are inconsistent and important safety concerns have been reported. Fecal microbiota transplantation and washed microbiota transplantation remain investigational and should not be used routinely outside controlled protocols. At present, microbiota-oriented management should prioritize evidence-based supportive measures, particularly early oral or enteral nutrition and rational antimicrobial use. Future studies should combine clinical outcomes with standardized microbiome, metabolome, barrier, and resistance endpoints to determine whether direct microbiota modulation can become a safe and reproducible component of personalized therapy.