Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut–pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids’ (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut–pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Expanding the ethnic and geographic spectrum of hereditary pancreatitis: first report of a Tibetan case with compound SPINK1 variants

Pancreatic repair after acute pancreatitis (AP) is essential for restoring tissue integrity, but the intrinsic mechanisms coordinating acinar plasticity and regeneration remain poorly understood. Aberrant Ca ^{2 +} signaling drives acinar injury, but whether Ca ^{2 +} ‐responsive effectors regulate post‐injury repair remains unclear. This study identifies calcium/calmodulin‐dependent protein kinase II δ (CaMKIIδ) as a repair‐associated regulator of pancreatic regeneration. Global Camk2d deletion delays repair after caerulein‐induced AP without altering initial injury severity. Bone marrow chimeras and pancreas‐specific Camk2d deletion further demonstrate that pancreatic, rather than bone marrow‐derived, CaMKIIδ is required for efficient tissue repair. Transcriptomic and ultrastructural analyses reveal that Camk2d deficiency disrupts endoplasmic reticulum (ER) homeostasis and enhances PERK‐dependent unfolded protein response activation. Camk2d ‐deficient pancreas shows impaired acinar‐to‐ductal metaplasia (ADM) programs in vivo and defective ADM formation in ex vivo 3D culture. Integrated proteomic and phosphoproteomic profiling of acinar‐derived ADM identifies ancient ubiquitous protein 1 (AUP1), an ER‐associated degradation regulator, as a previously unrecognized CaMKIIδ‐dependent substrate candidate. Functional analyses show that phosphorylation of the AUP1 S280‐containing serine‐rich region promotes K48‐linked ubiquitination and restrains PERK‐dependent ER stress under pancreatic stress conditions. These findings define a CaMKIIδ–AUP1 axis linking Ca ^{2 +} ‐responsive kinase activity to ER proteostasis, ADM formation and pancreatic repair.