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What is Celiac Disease? - Celiac Disease and Systemic Enzymes
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Monday, 17 January 2011 18:49

The rigidity of the lifestyle changes necessary to manage celiac disease has led to an increasing use of digestive enzymes as a means to alleviate symptoms and improve quality of life. Certain proteolytic (protein digesting) enzymes have been identified to have extremely beneficial actions when applied to the inflammation related to this condition. Digestive enzymes, taken with each meal, enter into the small intestine. Enzymes can then assist in the proper break down of food into nutrients and waste.

 

Celiac Disease and DPP IV Enzyme Activity

Contained within the cells that line the villi of the small intestine is a very important proteolytic enzyme, dipeptidyl dipeptidase IV (DPP IV). Celiac disease research has included the investigation of the role of DPP IV in the digestion of the portion of the protein found in gluten that is recognized as an “offender” by the immune system, also called an epitope.

The particular epitopes of concern in gliadin are rich in the amino acid proline. Studies show that endopeptidases, or enzymes that break protein bonds from within the molecule rather than at the ends, that are normally released by the pancreas do not effectively digest the epitopes. This suggests that DPP IV digestion in the small intestine is critical. Research has also found that DPP IV activity in patients with celiac disease is low and that they may not have the capacity to digest the protein after a gluten-rich meal, contributing to the development of the disease.1,2,3

One study on this enzyme compared two populations of rats, one with the intestinal DPP IV and one which genetically lacked the enzyme. The rats were fed diets high in proline-containing peptides for 4 weeks. The control group (with DPP IV) maintained body weight after 4 weeks on the diet, while the group lacking DPP IV experienced significant weight loss.  Evidence showed that the difference in the proteolytic activities between the two groups of rats was solely due to the absence of the DPP IV enzyme.4

Another study identified that specific mutation of the genes HLA-DQ2 and DQ8 can be linked to reduced amounts of DPP IV in Italian study group patients with celiac disease. The commonality of this gene mutation supports the establishment of the importance of DPP IV in gluten digestion and its absence in active celiac disease.5

Multiple investigations have identified the protein sequences of a small number of epitopes in gluten that account for the inflammatory response in celiac disease, indicating that they are highly resistant to digestion by proteases produced by the pancreas. Researchers looked at supplementing with DPP IV, as well as other prolyl (proline-specific) endopeptidases. They found that supplementing with DPP IV can compensate for the slow protein digestion, and that supplementing with additional proteases like prolyl endopeptidase (PEP), in combination with DPP IV, may be useful in reducing or even eliminating the inflammatory response related to gluten.6,7

Additionally, there is more evidence suggesting that taking a combination of proteases for gluten digestion is more beneficial than a single enzyme. In one study, activity of X-prolyl dipeptidyl aminopeptidase (X-PDAP), a non-specific DPP enzyme, was measured alone and in combination with another enzyme, non-specific monoanimopeptidase (AP). When AP was combined with subtilisin (a serine-specific endopeptidase), gluten digestion was measured at 47%. Upon adding X-PDAP, activity increased to 64%, suggesting a synergism in breaking down proteins when these enzymes are taken as a complex.8 Another study looked at the possibilities of a combination enzyme therapy in treating celiac disease. In vivo and in vitro (rat) experimental digestive systems were used and were treated with a glutamine-specific endoprotease (EP-B2) and a prolyl endopeptidase (SC PEP) enzyme product. The analysis revealed that EP-B2 extensively breaks down complex gluten proteins in bread, and SC PEP rapidly detoxifies the residual protein products of EP-B2 digestion. Researchers concluded that by combining 2 enzymes with normal digestive activity it should be possible to increase the safe threshold of ingested gluten, reducing the need for a highly restricted diet for celiac patients.9

Celiac Disease and Probiotics

Current research has found that probiotics, or live beneficial bacteria, can also play a large role in in reducing inflammation and symptoms of celiac disease. Many bacterial strains have been evaluated for their effects on protein digestion, as well as protection of the intestinal cells.

Much research has been conducted focusing on strains of bacteria used in slow fermentation when making sourdough bread, most notably Lactobacillus plantarum, and their implications for increased gluten tolerance in those with celiac disease. It has been found that selected sourdough lactobacilli are capable of breaking down offending gluten proteins, noticeably decreasing the toxicity of proline-rich epitopes, both in vitro and in vivo.10,11 Not only have these beneficial bacteria been studied for their use as ingested supplements, but also for their activity in food processing, providing new perspectives for manufacturing baked goods that are tolerated by celiac patients.12,13

Bacterial enzyme preparations and intact probiotic preparations have been shown to digest the gliadin epitopes known to play a role in celiac disease development, each working in slightly different ways.14,15,16 However, beyond reducing the risk of intestinal damage by working directly on protein fractions, probiotics have also been shown to directly alter the function of intestinal cells. One study looked at a probiotic preparation called VSL#3 for its ability to digest certain epitopes, but also found that it had the capacity to increase barrier function of the cells lining the intestinal tract, which may help to prevent epitopes from entering into the blood stream.15 Many other studies have replicated this effect while also demonstrating the ability of probiotics to stabilize the tight junctions between cells and prompt mucus secretion, which are protective mechanisms of the intestines.17 These protective mechanisms  shown by several probiotic strains have proved able to protect the intestinal lining from various offenses including infectious bacteria and inflammatory markers, or cytokines. 17,18,19,20

Supplementation with a variety of bacterial strains in a probiotic blend can help inhibit the gluten/gliadin-induced damage in the small intestine. Furthermore, probiotics may speed up recovery of damaged villi after adjusting to a gluten-free diet or provide protection to the small intestinal lining against hidden traces of gluten. Celiac disease patients could benefit immensely from the protection and promotion of intestinal health offered by probiotics.16

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References:

  1. Kozakova H, Steepankova R, Kolinska J, et al. Brush border enzyme activities in the small intestine after long-term gliadin feeding in animal models of human coeliac disease. Folia Microbiol (Praha). 1998; 43(5):497-500. 
  2. Koch S, Anthonsen D, Skovbjerg H, Sjöström H. On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease. Adv Exp Med Biol. 2003; 524:181-7. 
  3. Detel D, Persic M, Varljen J. Serum and Intestinal Dipeptidyl Peptidase IV (DPP IV/CD26) Activity in Children With Celiac Disease. J Ped Gast Nutr. 2007; 45(1):65-70. 
  4. Tiruppathi C, Miyamoto Y, Ganapathy V, Leiback FH. Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides. Am J Physiol. 1993; 265(1 pt 1):G81-9. 
  5. Clot F, Babron MC, Percopo S, et al. Study of Two Ectopeptidases in the Susceptibility to Celiac Disease: Two Newly Identified Polymorphisms of Dipeptidylpeptidase IV. J Ped Gast Nutr. 2000; 30(4):464-6. 
  6. Marti T, Molberg O, Li Q, et al. Prolyl Endopeptidase-Mediated Destruction of T Cell Epitopes in Whole Gluten: Chemical and Immunological Characterization. J Pharmacol Exp Ther. 2005; 312(1):19-26. 
  7. Hausch F, Shan L, Santiago NA, et al. Intestinal digestive resistance of immunodominant gliadin peptides.  Am J Physiol Gastrointest Liver Physiol. 2002; 283(4):G996-G1003. 
  8. Byun T, Kofod L, Blinkovsky A.Synergistic Action of an X-Prolyl Dipeptidyl Aminopeptidase and a Non-Specific Aminopeptidase in Protein Hydrolysis. J Agric Food Chem. 2001; 49(4):2061-3. 
  9. Gass J, Bethune MT, Siegel M, et al. Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue. Gastroent. 2007; 133(2):472-80. 
  10. Gobbetti M, Rizzello CG, Di Cagno R, De Angelis M. Sourdough lactobacilli and celiac disease. Food Microbiol. 2007; 24(2):187-196. 
  11. Klingberg TD, Pedersen MH, Cencic A, Budde BB. Application of Measurements of Transepithelial Electrical Resistance of Intestinal Epithelial Cell Monolayers to Evaluate Probiotic Activity. Appl Environ Microbiol. 2005; 71(11):7528-30. 
  12. Rollan G, De Angelis M, Gobbetti M, de Valdez GF. Proteolytic activity and reduction of gliadin-like fractions by sourdough lactobacilli. J Appl Microbiol. 2005; 99(6):1495-502. 
  13. Rizzello CG, De Angelis M, Di Cagno R, et al. Highly Efficient Gluten Degradation by Lactobacilli and Fungal Proteases during Food Processing: New Perspectives for Celiac Disease. Appl Environ Microbiol. 2007; 73(14):4499-4507. 
  14. Yan F, Cao H, Cover TL, et al. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenertology. 2007; 132(2):562-75. 
  15. De Angelis M, Rizzello CG, Fasano A, et al. VSL#3 probiotic preparation has the capacity to hydrolyze gliadin polypeptides responsible for Celiac Sprue. Biochem Biophys Acta. 2006; 1762(1):80-93. 
  16. Lindfors K, Blomqvist T, Juuti-Uusitalo K, et al. Live probiotic Bifidobacterium lactis bacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture. Clin Exp Immunol. 2008; 152(3):552-8. 
  17. Otte JM, Podolsky DK. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol. 2004; 286(4):G613-26. 
  18. Resta-Lenert S, Barrett KE. Live probiotics prtect intestinal epithelial cells from the effects of infection with enterovasasive Escherichia coli (EIEC). Gut. 2003; 52:988-97. 
  19. De Palma G, Cinova J, Stepankova R, et al. Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease. J Leukocyte Biol. 2010; 87(5):765-78. 
  20. D’Arienzo R, Maurano F, Lavermicocca P, et al. Modulation of the immune response by probiotic strains in a mouse model of gluten sensitivity. Cytokine. 2009; 48(3):254-9.

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Last Updated on Monday, 26 August 2013 19:06