20 July 2026 : Review article
The Roles of Gut Microbiota in the Pathogenesis of Acute Pancreatitis
Jun-Hua Ming BCDEF 1, Chang Chen EF 1, Jie Li D 1,2, Jie Gao E 1,2, Qing Zhang DG 1,2,3*DOI: 10.12659/MSM.952647
Med Sci Monit 2026; 32:e952647
Introduction
Gut Microbiota and Pancreatitis: A Bidirectional Relationship
Etiology-Specific Interactions With the Gut Microbiota
Mechanisms Linking Gut Microbiota Dysbiosis to Acute Pancreatitis
Intestinal Barrier Disruption and Bacterial Translocation
Roles of Microbial Metabolites
Regulation of the Gut Microbial-Metabolic-Immune Axis
Therapeutic Strategies Targeting Gut Microecology
Probiotics and Prebiotics
Antibiotic Therapy
Fecal Microbiota Transplantation
Enteral Nutrition
Traditional Chinese Medicine
Metagenomics and Metabolomics
Future Directions
Conclusions
References
Table 1 Mechanisms by which gut microbial metabolites affect acute pancreatitis.
| Metabolite | Mechanism of action | Impact on AP | References |
|---|---|---|---|
| Butyrate | Inhibits NLRP3 inflammasome activation; promotes regulatory T-cell function | Reduces intestinal barrier damage and inflammation, ameliorating AP | Pan et al []Xiao et al []50 |
| Vitamin D | Blocks NF-κB activation via VDR; inhibits apoptosis in intestinal epithelial cells | Protects intestinal barrier at moderate levels; excessive levels may exacerbate AP | Liu et al []52 |
| Bile acids, alcohol | Activates Orai1, leading to Ca overload and impaired ductal cell secretion | Increases pancreatic ductal cell necrosis, aggravating AP | Pallagi et al []54 |
| Hydrogen sulfide (H2S) | Activates K_ATP channels; increases TNF-α and IL-6 via the PI3K/Akt/Sp1 pathway | Proinflammatory effects, exacerbating AP | Liu et al []55 |
| Nicotinamide mononucleotide | Increases pancreatic NAD+ levels; activates SIRT3-PRDX5 pathway | Anti-inflammatory and antioxidant effects, reducing AP severity | Liu et al []56 |
| Docosahexaenoic acid | Inhibits JAK2/STAT3 pathway at low concentrations; activates PKC at high concentrations | Protective at low concentrations; exacerbates AP at high concentrations | Jeong et al []57 |
| Lactic acid | Lowers macrophage and neutrophil activity via TLR4/MyD88 and NLRP3/caspase-1 pathways | Reduces inflammation, ameliorating AP | Li et al []58 |
| Abbreviations: Akt, protein kinase B; AP, acute pancreatitis; JAK2, Janus kinase 2; IL-6, interleukin-6; MyD88, myeloid differentiation primary response 88; NAD, nicotinamide adenine dinucleotide; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family pyrin domain containing 3; Orai1, calcium-release-activated calcium channel protein 1; PI3K, phosphoinositide 3-kinase; PKC, protein kinase C; PRDX5, peroxiredoxin 5; SIRT3, sirtuin 3; Sp1, specificity protein 1; STAT3, signal transducer and activator of transcription 3; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha; VDR, vitamin D receptor. | |||