You Qian^{1, 2}, Miao Xiong^{1, 2}, Xin Gan^{1, 3}, Dan Xu⁴, Hejiang Zhou^{1, 3}, Ling-Yan Su^{1, 3}, Yalan Han^{1, 3,}

Pancreatitis is a destructive inflammatory condition with substantial morbidity. Although epidemiological studies link dietary patterns to pancreatitis, causality remains uncertain. This study applied bidirectional Mendelian randomization (MR) to examine the causal influence of dietary habits on pancreatitis and to identify potential mediating metabolites in blood and urine. Large-scale genetic datasets were analyzed, covering dietary intake patterns, relevant biomarkers, and multiple pancreatitis subtypes—including acute (AP), chronic (CP), alcohol-associated acute (AAP), and alcohol-associated chronic (ACP) pancreatitis. Results identified four dietary habits (dried fruit, fresh fruit, processed meat, and cereal intake) among the 15 tested that had significant causal effects on pancreatitis, without reverse causality. Notably, dried fruit consumption showed protective effects against AP (p < 0.00005, beta = -1.2401) and CP (p = 0.0032, beta=-1.0084), partially mediated by blood and urine gamma-glutamyltransferase (GGT). Mediation analysis revealed GGT showed the highest mediation proportion, accounting for 8.6% (CP, p = 0.0014) and 4.6% (AP, p = 0.0261) of this protective effect. Our MR study first discovered that the dried fruit intakes protect against pancreatitis, mediated by the blood and urine biomarkers GGT. These findings improve our understanding of how dietary patterns influence pancreatitis development and offer valuable insights for designing targeted nutritional prevention strategies.

Mendelian randomization, food intakes, blood and urine biomarkers, pancreatitis, mediation analysis