Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: https://www.sciepub.com/journal/jfnr Editor-in-chief: Prabhat Kumar Mandal
Open Access
Journal Browser
Go
Journal of Food and Nutrition Research. 2025, 13(11), 428-436
DOI: 10.12691/jfnr-13-11-3
Open AccessArticle

Dietary Influences on Pancreatitis Risk Mediated by Gamma-glutamyltransferase: A Bidirectional Mendelian Randomization Analysis Using UK Biobank and Finngen Datasets

You Qian1, 2, Miao Xiong1, 2, Xin Gan1, 3, Dan Xu4, Hejiang Zhou1, 3, Ling-Yan Su1, 3 and Yalan Han1, 3,

1College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan 650201, China

2Yunnan Provincial Laboratory of Precision Nutrition and Personalized Manufacturing, Yunnan Agricultural University, Kunming, Yunnan 650201, China;These authors contributed equally to this work

3Yunnan Provincial Laboratory of Precision Nutrition and Personalized Manufacturing, Yunnan Agricultural University, Kunming, Yunnan 650201, China

4Guang'anmen Hospital, China Academy of Chinese Medical Sciences (South Campus), Beijing, 100105, China

Pub. Date: December 01, 2025

Cite this paper:
You Qian, Miao Xiong, Xin Gan, Dan Xu, Hejiang Zhou, Ling-Yan Su and Yalan Han. Dietary Influences on Pancreatitis Risk Mediated by Gamma-glutamyltransferase: A Bidirectional Mendelian Randomization Analysis Using UK Biobank and Finngen Datasets. Journal of Food and Nutrition Research. 2025; 13(11):428-436. doi: 10.12691/jfnr-13-11-3

Abstract

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.

Keywords:
Mendelian randomization food intakes blood and urine biomarkers pancreatitis mediation analysis

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

Figure of 4

References:

[1]  Mao, X., Huang, C., Wang, Y., Mao, S., et al., Association between Dietary Habits and Pancreatitis among Individuals of European Ancestry: A Two-Sample Mendelian Randomization Study. Nutrients 2023, 15.
 
[2]  Xiao, A. Y., Tan, M. L., Wu, L. M., Asrani, V. M., et al., Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol 2016, 1, 45-55.
 
[3]  Boxhoorn, L., Voermans, R. P., Bouwense, S. A., Bruno, M. J., et al., Acute pancreatitis. Lancet 2020, 396, 726-734.
 
[4]  Khan, E., Chakrabarty, S., Shariff, S., Bardhan, M., Genetics and Genomics of Chronic Pancreatitis with a Focus on Disease Biology and Molecular Pathogenesis. Glob Med Genet 2023, 10, 324-334.
 
[5]  Sankaran, S. J., Xiao, A. Y., Wu, L. M., Windsor, J. A., et al., Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology 2015, 149, 1490-1500.e1491.
 
[6]  Yadav, D., O'Connell, M., Papachristou, G. I., Natural history following the first attack of acute pancreatitis. Am J Gastroenterol 2012, 107, 1096-1103.
 
[7]  Cai, Q. Y., Tan, K., Zhang, X. L., Han, X., et al., Incidence, prevalence, and comorbidities of chronic pancreatitis: A 7-year population-based study. World J Gastroenterol 2023, 29, 4671-4684.
 
[8]  Molero, X., Ayuso, J. R., Balsells, J., Boadas, J., et al., Chronic pancreatitis for the clinician. Part 1: Etiology and diagnosis. Interdisciplinary position paper of the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees. Gastroenterol Hepatol 2022, 45, 231-248.
 
[9]  Lukic, S., Mijac, D., Filipovic, B., Sokic-Milutinovic, A., et al., Chronic Abdominal Pain: Gastroenterologist Approach. Dig Dis 2022, 40, 181-186.
 
[10]  Park, W., Chawla, A., O'Reilly, E. M., Pancreatic Cancer: A Review. Jama 2021, 326, 851-862.
 
[11]  Guay, S. P., Gagnon, E., Paquette, M., Thériault, S., et al., Pancreatitis polygenic risk score is independently associated with all-cause acute pancreatitis risk in the UK Biobank. J Gastroenterol Hepatol 2024.
 
[12]  Yadav, D., Lowenfels, A. B., The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013, 144, 1252-1261.
 
[13]  Oskarsson, V., Sadr-Azodi, O., Orsini, N., Andrén-Sandberg, Å., Wolk, A., Vegetables, fruit and risk of non-gallstone-related acute pancreatitis: a population-based prospective cohort study. Gut 2013, 62, 1187-1192.
 
[14]  Oskarsson, V., Sadr-Azodi, O., Orsini, N., Andrén-Sandberg, Å., Wolk, A., High dietary glycemic load increases the risk of non-gallstone-related acute pancreatitis: a prospective cohort study. Clin Gastroenterol Hepatol 2014, 12, 676-682.
 
[15]  Oskarsson, V., Orsini, N., Sadr-Azodi, O., Wolk, A., Fish consumption and risk of non-gallstone-related acute pancreatitis: a prospective cohort study. Am J Clin Nutr 2015, 101, 72-78.
 
[16]  Oskarsson, V., Sadr-Azodi, O., Orsini, N., Wolk, A., A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis. Br J Nutr 2016, 115, 1830-1834.
 
[17]  Setiawan, V. W., Pandol, S. J., Porcel, J., Wei, P. C., et al., Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort. Clin Gastroenterol Hepatol 2017, 15, 257-265.e253.
 
[18]  Mao, X., Mao, S., Sun, H., Huang, F., et al., Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study. Front Immunol 2023, 14, 1091780.
 
[19]  Hansen, S. E. J., Madsen, C. M., Varbo, A., Tybjærg-Hansen, A., Nordestgaard, B. G., Genetic Variants Associated With Increased Plasma Levels of Triglycerides, via Effects on the Lipoprotein Lipase Pathway, Increase Risk of Acute Pancreatitis. Clin Gastroenterol Hepatol 2021, 19, 1652-1660.e1656.
 
[20]  Hansen, S. E. J., Langsted, A., Varbo, A., Madsen, C. M., et al., Low and high pancreatic amylase is associated with pancreatic cancer and chronic pancreatitis. Eur J Epidemiol 2021, 36, 975-984.
 
[21]  Zhou, C. L., Zhang, C. H., Zhao, X. Y., Chen, S. H., et al., Early prediction of persistent organ failure by serum apolipoprotein A-I and high-density lipoprotein cholesterol in patients with acute pancreatitis. Clin Chim Acta 2018, 476, 139-145.
 
[22]  Stirling, A. D., Moran, N. R., Kelly, M. E., Ridgway, P. F., Conlon, K. C., The predictive value of C-reactive protein (CRP) in acute pancreatitis - is interval change in CRP an additional indicator of severity? HPB (Oxford) 2017, 19, 874-880.
 
[23]  Birney, E., Mendelian Randomization. Cold Spring Harb Perspect Med 2022, 12.
 
[24]  Sun, J. X., Xu, J. Z., Liu, C. Q., An, Y., et al., The association between human papillomavirus and bladder cancer: Evidence from meta-analysis and two-sample mendelian randomization. J Med Virol 2023, 95, e28208.
 
[25]  Wang, C., Zhu, D., Zhang, D., Zuo, X., et al., Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study. BMC Psychiatry 2023, 23, 590.
 
[26]  Sudlow, C., Gallacher, J., Allen, N., Beral, V., et al., UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015, 12, e1001779.
 
[27]  Sinnott-Armstrong, N., Tanigawa, Y., Amar, D., Mars, N., et al., Genetics of 35 blood and urine biomarkers in the UK Biobank. Nat Genet 2021, 53, 185-194.
 
[28]  Burgess, S., Scott, R. A., Timpson, N. J., Davey Smith, G., Thompson, S. G., Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol 2015, 30, 543-552.
 
[29]  Naderi, M., Salavatiha, Z., Gogoi, U., Mohebbi, A., An overview of anti-Hepatitis B virus flavonoids and their mechanisms of action. Front Cell Infect Mi 2024, 14.
 
[30]  Yang, J., Yan, B., Zhao, B., Fan, Y., et al., Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders. Schizophr Bull 2020, 46, 804-813.
 
[31]  Ran, B., Qin, J., Wu, Y., Wen, F., Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study. Expert Rev Clin Immunol 2024, 20, 413-421. Yuan, J., Xiong, X., Zhang, B., Feng, Q., et al., Genetically predicted C-reactive protein mediates the association between rheumatoid arthritis and atlantoaxial subluxation. Front Endocrinol (Lausanne) 2022, 13, 1054206.
 
[32]  Choi, K. W., Chen, C. Y., Stein, M. B., Klimentidis, Y. C., et al., Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults: A 2-Sample Mendelian Randomization Study. JAMA Psychiatry 2019, 76, 399-408.
 
[33]  Cheng, Z. X., Hua, J. L., Jie, Z. J., Li, X. J., Zhang, J., Genetic Insights into the Gut-Lung Axis: Mendelian Randomization Analysis on Gut Microbiota, Lung Function, and COPD. Int J Chron Obstruct Pulmon Dis 2024, 19, 643-653.
 
[34]  Pierce, B. L., Burgess, S., Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol 2013, 178, 1177-1184.
 
[35]  Davies, N. M., Holmes, M. V., Davey Smith, G., Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. Bmj 2018, 362, k601.
 
[36]  Larsson, S. C., Traylor, M., Malik, R., Dichgans, M., et al., Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis. Bmj 2017, 359, j5375.
 
[37]  Cai, J., Li, X., Wu, S., Tian, Y., et al., Assessing the causal association between human blood metabolites and the risk of epilepsy. J Transl Med 2022, 20, 437.
 
[38]  Carter, A. R., Sanderson, E., Hammerton, G., Richmond, R. C., et al., Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur J Epidemiol 2021, 36, 465-478.
 
[39]  Jouvet, N., Estall, J. L., The pancreas: Bandmaster of glucose homeostasis. Exp Cell Res 2017, 360, 19-23.
 
[40]  Capurso, G., Traini, M., Piciucchi, M., Signoretti, M., Arcidiacono, P. G., Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol 2019, 12, 129-139.
 
[41]  Whitcomb, D. C., Lowe, M. E., Human pancreatic digestive enzymes. Dig Dis Sci 2007, 52, 1-17.
 
[42]  Kinouchi, T., Koyama, S., Harada, E., Yajima, T., Large molecule protein feeding during the suckling period is required for the development of pancreatic digestive functions in rats. Am J Physiol Regul Integr Comp Physiol 2012, 303, R1268-1276.
 
[43]  Liu, R. H., Health-promoting components of fruits and vegetables in the diet. Adv Nutr 2013, 4, 384s-392s.
 
[44]  Rampersaud, G. C., Valim, M. F., 100% citrus juice: Nutritional contribution, dietary benefits, and association with anthropometric measures. Crit Rev Food Sci Nutr 2017, 57, 129-140.
 
[45]  Alasalvar, C., Salvadó, J. S., Ros, E., Bioactives and health benefits of nuts and dried fruits. Food Chem 2020, 314, 126192.
 
[46]  Sadler, M. J., Gibson, S., Whelan, K., Ha, M. A., et al., Dried fruit and public health - what does the evidence tell us? Int J Food Sci Nutr 2019, 70, 675-687.
 
[47]  Bolling, B. W., Aune, D., Noh, H., Petersen, K. S., Freisling, H., Dried Fruits, Nuts, and Cancer Risk and Survival: A Review of the Evidence and Future Research Directions. Nutrients 2023, 15.
 
[48]  Kountouri, A. M., Gioxari, A., Karvela, E., Kaliora, A. C., et al., Chemopreventive properties of raisins originating from Greece in colon cancer cells. Food Funct 2013, 4, 366-372.
 
[49]  Chen, Z. J., Yang, Y. F., Zhang, Y. T., Yang, D. H., Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L. Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer's Markers in SAMP8 Mice. Molecules 2018, 23.
 
[50]  Kowalska, J., Kowalska, H., Marzec, A., Brzeziński, T., et al., Dried strawberries as a high nutritional value fruit snack. Food Sci Biotechnol 2018, 27, 799-807.
 
[51]  Donno, D., Mellano, M. G., Riondato, I., De Biaggi, M., et al., Traditional and Unconventional Dried Fruit Snacks as a Source of Health-Promoting Compounds. Antioxidants (Basel) 2019, 8.
 
[52]  Di Lorenzo, C., Sangiovanni, E., Fumagalli, M., Colombo, E., et al., Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study. Int J Mol Sci 2016, 17.
 
[53]  Chaiwong, S., Chatturong, U., Chanasong, R., Deetud, W., et al., Dried mulberry fruit ameliorates cardiovascular and liver histopathological changes in high-fat diet-induced hyperlipidemic mice. J Tradit Complement Med 2021, 11, 356-368.
 
[54]  Kunutsor, S. K., Gamma-glutamyltransferase-friend or foe within? Liver Int 2016, 36, 1723-1734.
 
[55]  Lieberman, M. W., Wiseman, A. L., Shi, Z. Z., Carter, B. Z., et al., Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. Proc Natl Acad Sci U S A 1996, 93, 7923-7926.
 
[56]  Pucci, A., Franzini, M., Matteucci, M., Ceragioli, S., et al., b-Gamma-glutamyltransferase activity in human vulnerable carotid plaques. Atherosclerosis 2014, 237, 307-313.
 
[57]  Koenig, G., Seneff, S., Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk. Dis Markers 2015, 2015, 818570.
 
[58]  Corti, A., Franzini, M., Paolicchi, A., Pompella, A., Gamma-glutamyltransferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting. Anticancer Res 2010, 30, 1169-1181.
 
[59]  Terzyan, S. S., Burgett, A. W., Heroux, A., Smith, C. A., et al., Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS. J Biol Chem 2015, 290, 17576-17586.