Original article Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats Q5 Mark C. van Baal a , Michiel J. van Rens a , Christopher B. Geven a , Francien M. van de Pol b , Ilona W. van den Brink b , Gerjon Hannink a , Iris D. Nagtegaal c , Wilbert H. Peters d , Ger T. Rijkers a , Hein G. Gooszen a, * a Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands b Dept. of Anesthesiology, Radboudumc, Nijmegen, The Netherlands c Dept. of Pathology, Radboudumc, Nijmegen, The Netherlands d Dept. of Gastroenterology, Radboudumc, Nijmegen, The Netherlands article info Article history: Available online xxx Keywords: Acute pancreatitis Probiotics Prophylaxis Enteral nutrition Bowel ischaemia Bacterial translocation abstract Background/objectives: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic prophylaxis and enteral nutrition contributed to the higher mortality rate. Methods: Male SpragueeDawley rats were allocated to four groups: 1) acute pancreatitis (n ¼ 9), 2) acute pancreatitis and probiotic prophylaxis (n ¼ 10), 3) acute pancreatitis and enteral nutrition (n ¼ 10), and 4) acute pancreatitis, probiotic prophylaxis and enteral nutrition (n ¼ 11). Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Enteral nutrition, saline, probiotics and placebo were administered through a permanent jejunal feeding. Probiotics or placebo were administered starting 4 days before induction of pancreatitis and enteral nutrition 1 day before start until the end of the experiment, 6 days after induction of pancreatitis. Tissue samples and body fluids were collected for microbiological and histological examination. Results: In all animals, serum amylase was increased six hours after induction of pancreatitis. After fulfilling the experiment, no differences between groups were found in histological severity of pancre- atitis, degree of discomfort, weight loss, histological examination of small bowel and bacterial trans- location (all p > 0.05). Overall mortality was 10% without differences between groups (p ¼ 0.54). Conclusion: No negative association was found between prophylactic probiotics and enteral nutrition in acute pancreatitis. No new clues for a potential mechanism responsible for the higher mortality and bowel ischaemia in the PROPATRIA study were found. Copyright © 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Introduction Acute pancreatitis runs a mild course in the majority of patients. However, 20% of patients develop a severe pancreatitis with the presence of peripancreatic or pancreatic necrosis and (multiple) organ failure [1]. If the necrosis becomes infected, this is associated with a mortality of 15e25% and a morbidity rate of 50e100% [2e5]. Infection of necrotic pancreatic tissue is caused by bacterial trans- location from the intestines and is thought to be preceded by three pathophysiological processes: 1) bacterial overgrowth of the small bowel due to decreased bowel motility, 2) dysfunction of the local mucosal and systemic immune system, and 3) increased intestinal permeability, resulting in bacterial translocation to other sites, such as the pancreas [6e8]. Reduction of bacterial translocation may reduce the rate of secondary infection of the pancreatic necrosis and decrease mortality and morbidity. In 2006, our study group started a multicenter placebo- controlled randomized trial (PROPATRIA) on probiotic prophylaxis in patients with predicted severe pancreatitis [9]. Based on the results of a smaller trial, the aim of the study was to reduce the * Corresponding author. Radboudumc, Nijmegen, PO Box 9101, HP 690, 6500 MB Nijmegen, The Netherlands. Q1 E-mail addresses: markvanbaal@gmail.com (M.C. van Baal), hein.gooszen@ radboudumc.nl (H.G. Gooszen). Contents lists available at ScienceDirect Pancreatology journal homepage: www.elsevier.com/locate/pan http://dx.doi.org/10.1016/j.pan.2014.10.002 1424-3903/Copyright © 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Pancreatology xxx (2014) 1e8 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 PAN323_proof ■ 20 October 2014 ■ 1/8 Please cite this article in press as: van Baal MC, et al., Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats, Pancreatology (2014), http://dx.doi.org/10.1016/j.pan.2014.10.002