Dietary and Lifestyle Risk Factors in Primary Sclerosing Cholangitis: In Search of Mechanistic Explanations and...

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated liver disease characterized by progressive inflammation and fibrosis of the bile ducts. Although much of the research has focused on genetic and autoimmune mechanisms, growing interest has emerged in the role of modifiable risk factors, including dietary and lifestyle factors, in the pathogenesis and progression of PSC. This review aims to provide a comprehensive synthesis of the current literature on dietary and lifestyle influences on PSC, with particular attention to underlying molecular pathways. Key factors discussed include smoking, alcohol consumption, physical activity, and medical history factors such as appendectomy, tonsillectomy, and hormonal therapies. Additionally, the review explores the impact of dietary components, such as coffee, vitamins, probiotics, and dietary fibers, on PSC progression. Potential mechanisms highlighted include alterations in bile acid metabolism, gut microbiota dysbiosis, disruption of intestinal barrier integrity, and modulation of innate and adaptive immune responses through cytokine signaling and pattern recognition receptor pathways. Emerging evidence also suggests that coffee constituents may influence oxidative stress pathways and fibrogenesis, whereas dietary fibers and probiotics may act through short-chain fatty acid production and anti-inflammatory signaling. Although the evidence for many of these factors remains inconclusive, these molecular insights point to diet-induced immunometabolism modulation as a promising area for therapeutic intervention. Further prospective studies and randomized trials are needed to clarify these mechanisms and develop targeted strategies to modify disease onset and progression.