Digestion and Detoxification

Dogs with exocrine pancreatic insufficiency (EPI) secrete inadequate amount of essential digestive enzymes, which can lead to malabsorption and maldigestion.

PANCREATIC ELASTASE 1 (PE1)

What is it:
Dogs with exocrine pancreatic insufficiency (EPI) secrete inadequate amounts of essential digestive enzymes which can lead to malabsorption and maldigestion. Clinically it can be manifested by anorexia, digestive disturbances, weight loss and loss of general body condition. Maldigestion symptoms include, diarrhea, weight loss, and altered appetite. Maldigestion can lead to low nutrient levels such as fat-soluble vitamins such as vitamin D, E, A and K, or fatty acids such as EPA and DHA. Low levels of these nutrients have been associated with dry skin and other health conditions. Thus, symptoms can be varied.

Fecal fat output was significantly higher in dogs with malabsorption or pancreatic insufficiency than in clinically normal dogs, dogs with colitis, or dogs with non-steatorrhea diarrheas.[1-3]  

A single fecal elastase concentration of 20 µg/g has been used to EPI in dogs with chronic diarrhea. In research laboratories a value of 10 µg/g or 20 µg/g along with typical clinical signs is suggestive of pancreatic dysfunction. Research has noted the sensitivity from 95-96%  and specificity of 85 to 92%.[4] Values > 40 µg/g feces indicate normal exocrine pancreatic function. The test is not impacted by enzyme supplementation. Reference ranges set by IPL:

  • Normal: >30 µg/g
  • Borderline: 20-30 µg/g
  • Low: <20 µg/g

EPI prevalence has been noted by breed, in 2007 research utilizing abnormally low serum canine trypsin‐like immunoreactivity (cTLI) concentration for diagnosis.[5]

  • Breed with a higher rate of PEI: Chow, German Shepard, Cavalier King Charles Spaniel, West Highland White Terrier, Cairn Terrier, Cocker Spaniel, Rough-coat Collie.
  • Breeds with a lower rate of PEI: Boxer, Golden and Labrador Retrievers, Great Dane, Rottweiler, and

Causes of lower Elastase:
The most common cause of EPI in dogs is pancreatic acinar atrophy, an immune-mediated condition that begins with lymphocytic pancreatitis. As in people diabetes has also been associated with increased risks of EPI. Though less common pancreatic neoplasia (cancer) can also be a cause.[6] [7]

Figure 1: Vet Med Sci. 2021 Nov; 7(6): 2144–2155.

As noted in Figure 1, significantly lower fecal sIgA concentrations and a low serum canine trypsin‐like immunoreactivity (cTLI) concentration was consistent with a diagnosis of EPI.[8] 

Treatments:

  • Support with digestive enzymes. Pancreatic enzyme replacement therapy is the standard treatment for dogs with EPI and consists of mixing commercially available pancreatic enzyme supplements with meals. Research has noted that there was no difference between enzyme enteric coated and uncoated enzyme replacement.[9]
  • Evaluate and support as needed: fats DHA and EPA, and fat-soluble vitamins A, D, E and K
  • Consider a therapeutic meal plan, such as a prescription diet dog food.
  • Consider checking level of fecal sIgA as levels have been noted as lower in dogs with EPI.[8]
  • Minimizing anxiety and stress.
BETA-GLUCURONIDASE  

What is it:
Beta-glucuronidase is an enzyme produced by most mammalian colon cells and anaerobic gut bacteria. Some GI bacterial strains exhibit enzyme activities, including beta-glucuronidase activity, which has been associated with intestinal diseases. Thus levels may be produced by the host or gut bacteria. It is a biologically active enzyme that breaks down complex carbohydrates for better absorption. When Beta-glucosidases breaks down carbohydrates it makes plant polyphenols more bioavailability, which is good, and it also helps to extract extra energy from indigestible carbohydrates (insoluble fibers). It also deconjugates xenobiotic, such as toxins, carcinogens, hormones, and drugs that have previously gone through glucuronidation via phase II detoxification, allowing them to be unconjugated within the intestines. Beta-glucuronidases are believed to be an important and critical component in the cleavage of xenobiotic compounds and conjugated hormone. Excessively high levels may be associated with an imbalanced intestinal microbiota, and may lead to inflammation and GI damage. It is a balance of level of Beta-glucuronidase, gut microbiota, level of toxin exposure and diet.[10]

Causes of impaired levels:

  • Low levels have been noted in groups with Inflammatory bowel disease, compared to healthy. Low beta-glucuronidase activity is an indicator of abnormal metabolic activity among the intestinal microbiota.
  • A high level of beta-glucuronidase may identify increased detoxification of toxins, carcinogens or hormones.
    • A potential dietary carcinogen derived from cooked meat and fish induces high Beta-glucuronidase activity and prolongs internal exposure to the toxin in an experimental animal model. Higher beta-glucuronidase may be associated with an imbalanced intestinal microbiota profile. 

Treatments:

  • Support a healthy gut microbiota with diet or probiotics.
    • Fecal beta-glucuronidase, beta-galactosidase was decreased in dogs fed the dry diet, compared to can. The authors note that canned dog food led to reduced lactobacillus and bifidobacteria and increased Clostridia.[11]
  • Support with beta-glucan supplement if low, such as a mushroom complex.
  • Evaluate toxin exposure or hormone levels.
  • Consider targeted supplements.
    • In animal studies supplementation of fenugreek seeds in the diet modulated the activities of beta-glucuronidase. Beta-glucuronidase activity reduced with psyllium (ispaghula) supplementation.[12, 13]
  • Minimizing anxiety and stress

References:

  1. Burrows, C.F., A.M. Merritt, and A.M. Chiapella, Determination of fecal fat and trypsin output in the evaluation of chronic canine diarrhea. J Am Vet Med Assoc, 1979. 174(1): p. 62-6.
  2. Spillmann, T., E. Eigenbrodt, and A. Sziegoleit, [Determination and clinical relevance of fecal pancreatic elastase in dogs]. Tierarztl Prax Ausg K Kleintiere Heimtiere, 1998. 26(5): p. 364-8.
  3. Piccione, G., et al., Blood lipids, fecal fat and chymotrypsin excretion in the dog: influence of age, body weight and sex. J Vet Med Sci, 2004. 66(1): p. 59-62.
  4. Singh, A.K., Exocrine pancreatic insufficiency in canines: An update. JOURNAL OF ENTOMOLOGY AND ZOOLOGY STUDIES 2018. 6(5): p. 854-858.
  5. Batchelor, D.J., et al., Breed associations for canine exocrine pancreatic insufficiency. J Vet Intern Med, 2007. 21(2): p. 207-14.
  6. Watson, P.J., Exocrine pancreatic insufficiency as an end stage of pancreatitis in four dogs. J Small Anim Pract, 2003. 44(7): p. 306-12.
  7. DVM360. A quick review of canine exocrine pancreatic insufficiency. 2009; Available from: https://www.dvm360.com/view/veterinary-practice-management-software-options.
  8. Grutzner, N., et al., Genomic association and further characterisation of faecal immunoglobulin A deficiency in German Shepherd dogs. Vet Med Sci, 2021. 7(6): p. 2144-2155.
  9. Parambeth, J.C., et al., Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency. J Vet Intern Med, 2018. 32(5): p. 1591-1599.
  10. Kubasova, I., et al., Evaluation of enterococci for potential probiotic utilization in dogs. Folia Microbiol (Praha), 2019. 64(2): p. 177-187.
  11. Martineau, B. and D.P. Laflamme, Effect of diet on markers of intestinal health in dogs. Res Vet Sci, 2002. 72(3): p. 223-7.
  12. Devasena, T. and V.P. Menon, Fenugreek affects the activity of beta-glucuronidase and mucinase in the colon. Phytother Res, 2003. 17(9): p. 1088-91.
  13. Wynn, S.G., Fougère, BJ., Veterinary Herbal Medicine: A Systems-Based Approach. Veterinary Herbal Medicine, 2009: p. 291–409.