In the complex progression of fibrosis in chronic pancreatitis, pancreatic stellate cells (PSCs) emerge as central figures. These cells, initially in a dormant state characterized by the storage of vitamin A lipid droplets within the chronic pancreatitis microenvironment, undergo a profound transformation into an activated state, typified by the secretion of an abundant extracellular matrix, including α-smooth muscle actin (α-SMA). This review delves into the myriad factors that trigger PSC activation within the context of chronic pancreatitis. These factors encompass alcohol, cigarette smoke, hyperglycemia, mechanical stress, acinar cell injury, and inflammatory cells, with a focus on elucidating their underlying mechanisms. Additionally, we explore the regulatory factors that play significant roles during PSC activation, such as TGF-β, CTGF, IL-10, PDGF, among others. The investigation into these regulatory factors and pathways involved in PSC activation holds promise in identifying potential therapeutic targets for ameliorating fibrosis in chronic pancreatitis. We provide a summary of recent research findings pertaining to the modulation of PSC activation, covering essential genes and innovative regulatory mediators designed to counteract PSC activation. We anticipate that this research will stimulate further insights into PSC activation and the mechanisms of pancreatic fibrosis, ultimately leading to the discovery of groundbreaking therapies targeting cellular and molecular responses within these processes.

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.

Introduction: Recurrence of acute pancreatitis (AP) is common, leading to cumulative pancreatic injury and reduced quality of life. While aetiology-based treatments and lifestyle interventions are effective, long-term adherence is often poor due to insufficient health awareness and a lack of continuous reminders. We designed the PROGRESS ( PRO active GR ad E d follow-up S trategy for reducing recurrence in acute pancreatiti S ) trial to evaluate whether a physician-initiated, proactive and graded follow-up strategy can reduce AP recurrence. Methods and analysis: The PROGRESS trial is a multicentre, open-label, randomised controlled trial. A total of 194 patients with AP will be randomised 1:1 to either a proactive follow-up group or a standard follow-up group. In the proactive follow-up group, patients are stratified into high-risk or low-risk categories based on reported risk factors. Follow-up is conducted via WeChat with varying frequencies: every 3 months for the high-risk group and every 6 months for the low-risk group. The standard follow-up group receives routine discharge education and a 1-month outpatient visit. The primary endpoint is the number of AP recurrence episodes within 24 months post-discharge. Secondary endpoints include AP recurrence rate, progression to chronic pancreatitis, quality of life (Short Form 12 Health Survey), anxiety/depression scores (Generalized Anxiety Disorder-7/Patient Health Questionnaire-9), readmission rates and mortality. Analysis will follow the intention-to-treat principle. Ethics and dissemination: This study has been approved by the Ethics Committee of Peking Union Medical College Hospital (No. I-25PJ2556, I-26PJ0895). Ethics approval of each participating centre is required before initiation of patient enrolment. The results of this study will be published in peer-reviewed journals. Trial registration number: ChiCTR2500113459 (Chinese Clinical Trial Registry).