Novel potential of pancreatic-like enzymes of microbial origin in exocrine pancreatic insufficiency – study on a pig model
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Department of Biology, Lund University, Sweden
R&D Vitanano, Lublin, Poland
Bogomoletz Institute of Physiology, Kiev, Ukraine
Department of Toxicology and Environmental Protection, University of Live Sciences, Lublin, Poland
Department of Biophysics and Biochemistry, National University, Dnepropetrovsk, Ukraine
Departmet of Technology and Food Quality Evaluation, Medical University of Silesia, Katowice, Poland
Department of Medical Biology, Institute of Rural Health, Lublin, Poland
Corresponding author
Stefan Pierzynowski   

Dept Biology, Lund University, Sölvegatan 35, 22362 Lund, Sweden
J Pre Clin Clin Res. 2015;9(1):5-10
The standard porcine-derived pancreatic enzyme replacement therapy (PERT) is a lifesaving treatment for patients with diseases causing exocrine pancreatic insufficiency (EPI). An attempt to replace PERT with microbial enzymes were undertaken. The aim was to highlight whether the mode of application, mixed with food or applied directly to the stomach, of pancreatic-like enzymes of microbial origin (PLEM) can affect their activity along the gastrointestinal tract.

Material and Methods:
The activity of amylase, lipase and proteinase in the stomach, duodenum and ileum were tested in EPI pigs (n=6) after supplementation of PLEM, either orally – before and during feed consumption – or via the stomach – before and during feed consumption. Healthy pigs not treated with PLEM (n=3) served as controls. Activity of the enzymes measured in the chyme were obtained together with the digesta pH. Activity of the enzymatic residues in the stool samples was also checked.

The highest pancreatic enzyme activities were found in the duodenum of the healthy pigs (amylase 162,68 kU/mL, lipase 507,34 kU/mL and protolitic (trypsin) activity 357,60 kU/mL). Nevertheless, the microbial enzymes remained also active along the entire length of the GIT – including stomach in EPI pigs, regardless of their route of administration. However, activity level was significantly lower.

Results indicate that the activity pattern of PLEM in the small intestine mimics the activity of the natural endogenous pancreatic enzymes in healthy pigs. The most physiological features of PLEM were observed when enzymes were offered orally. The magnitude of PLEM activity in the stomach of EPI pigs was essential and significantly higher than that measured in healthy pigs, thus being somewhat not physiological, and for health reasons of the patients should be further explored. Interestingly, specific trypsin-like activity was measured in all parts of the GIT after PLEM application. However, proteolytic activity of the experimental proteaze in in vitro studies did not exhibit trypsin-like activity.

Zingg U, Oertli D. Functional syndromes after surgery of the upper gastrointestinal tract. Ther Umsch. 2012; 69: 39–47.
Zoppi G, Andreotti G, Pajno-Ferrara F, Njai DM, Gaburro D. Exocrine pancreas function in pre-mature and full term neonates. Pediatr Res. 1972; 96: 880–886.
Jensen C, Buist NR, Wilson T. Absorption of individual fatty acids from long chain or medium chain triglyceride in very small infants. Am J Clin Nutr. 1986; 43: 745–751.
Majumdar AN, Jaszewski R, Dubick MA. Effect of aging on the gastrointestinal tract and the pancreas. Proc Soc Exp Biol Med. 1997; 215: 134–144.
Al-Kaade S. Exocrine pancreatic insufficiency. Medscape Reference. Drugs, Diseases & Procedures (access: 2013.10).
Safdi M, Bekal PK, Martin S, Saeed Z, Burton F, Toskes PP. The effect of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea. Pancreas. 2006; 33: 156–162.
Roxas M. The role of enzyme supplementation in digestive disorders. Altern Med Rev. 2008; 13: 307–314.
Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin Exp Gastroenterol. 2011; 4: 55–73.
Kalnins D, Ellis L, Corey M, Pencharz PB, Stewart C, Tullis E, et al. Enteric-coated pancreatic enzymes with bicarbonate is equal to standard enetric-coated enzyme in treating malabsorption in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2006; 42: 256–261.
Borowitz D, Stevens C, Brettman LR, Campion M, Wilschanski M, Thompson H. Liprotamase long-term safety and support of nutritional status in pancreatic-insufficient cystic fibrosis. J Pediatr Gastroenterol Nutr. 2012; 54: 248–457.
Thorat V, Reddy N, Bhatia S, Bapaye A, Rajkumar JS, Kini DD, et al. Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis – a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2012; 36: 426–436.
Aghdassi AA, Mayerle J, Christochowitz S, Weiss FU, Sendler M, Lerch MM. Animal models for investigating chronic pancreatitis. Fibrogenesis Tissue Repair. 2011; 4(1): 26.
Cummings JH, Jenkins DJA, Wiggins HS. Measurement of the mean transit time of dietary residue through the human gut. Gut 1976; 17: 210–218.
Castle EJ, Castle ME. The rate of passage of food through the alimentary tract of pigs. J Agric Sci. 1956; 47: 196–204.
Donaldson J, Fed`kiv O, Pawłowska M, Kowalik S, Erlwanger KH, Westrom B, et al. The effectiveness of enzymatic replacement therapy measured by turbidimetry and the lipaemic index in exocrine pancreatic insufficient young, growing pigs, fed a high-fat diet. Adv Med Sci. 2009; 54: 7–13.
Carr J. Garth Pig Stockmanship Standards. 5M Enterprises, UK. 1998.
Fedkiv O, Rengman S, Westrom BR, Pierzynowski SG. Growth is dependent on the exocrine pancreas function in young weaners but not in growing finishing pigs. J Physiol Pharmacol. 2009; 60: 55–59.
Pierzynowski S, Szwiec K, Piedra JLV, Gruijc D, Szymanczyk S, Swieboda P et al. Exogenous pancreatic-like enzymes are recovered in the gut and improve growth of exocrine pancreatic insufficient pigs. J Anim Sci. 2012; 90: 324–326.
Fritz H, Hartwich G, Werle E. On protease inhibitors. I. Isolation and characterization of trypsin inhibitors from dog pancreas tissue and pancreas scretion. Hoppe Seylers Z Physiol Chem. 1966; 345: 150–167.
Kuhn RJ, Gelrud A, Munck A, Caras S. CREON (Pancrelipase Delayed-Release Capsules) for the treatment of exocrine pancreatic insufficiency. Adv Ther. 2010; 27(12): 895–916.
Snoeck V, Huyghebaert N, Cox E, Vermeire A, Saunders J, Remon JP, et al. Gastrointestinal transit time of nondisintegrating radio-opaque pellets in suckling and recently weaned piglets. J Control Release. 2004; 94: 143–153.
Owyang C, Louie DS, Tatum D. Feedback regulation of pancreatic enzyme secretion. J Clin Invest. 1986; 77: 2042–4047.
Konturek SJ, Pepera J, Zabielski K, Konturek PC, Pawlik T, Szlachcic A, et al. Brain-gut axis in pancreatic secretion and appetite control. J Physiol Pharmacol. 2003; 54: 293–317.
DiMagno EP, Malagelada JR, Go VL, Moertel CG. Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. N Engl J Med. 1977; 196: 1318–1322.
Konturek PC, Brzozowski T, Konturek SJ. Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol. 2011; 60: 139–150.
Carriere F, Barrowman JA, Verger R, Laugier R. Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterol. 1993; 105: 876–888.
Sikkens ECM, Cahen DL, Kuipers EJ, Bruno MJ. Pancreatic enzyme replacement therapy in chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2010; 24: 337–347.
Pierzynowski S, Swieboda P, Filip R, Szwiec K, Piedra JLV, Gruijc D et al. Behavioral changes in response to feeding pancreatic-like enzymes to exocrine pancreatic insufficiency pigs. J Anim Sci. 2012; 90: 439–441.
Drozdowski L, Thomson ABR. Intestinal mucosal adaptation. World J Gastroenterol. 2006; 12: 4614–4627.
Slupecka M, Wolinski J, Prykhodko O, Ochniewicz P, Gruijc D, Fedkiv O, et al. Stimulating effect of pancreatic-like enzymes on the development of the gastrointestinal tract in piglets. J Agric Sci. 2012; 90: 311–314.
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