Intestinal Permeability: Leaky Gut

“Leaky gut syndrome is a term that is used to describe an increase in the permeability of the intestines.”

– Catherine Barnette, DVM[1]

ZONULIN

What is it:
Fecal zonulin is a tight junction protein linked to intestinal barrier integrity and is proposed as a clinically useful marker of intestinal permeability, as high levels can identify increased permeability, the breakdown of the tight junctions between intestinal epithelial cells. Zonulin is a physiological mediator of paracellular intestinal permeability and works by modulating intercellular tight junctions. Increased intestinal permeability is associated with increased intestinal inflammation and dysbiosis. Zonulin was found to be increased in intestinal biopsies of dogs with inflammatory bowel disease (IBD), as a risk factor for canine food , a player in a subset of dogs with atopic dermatitis, and in canine intestinal lymphangiectasia.[2, 3] Probiotic therapy was associated with upregulated expression of tight junction proteins, E-cadherin, occludin, and zonulin. In humans a powerful trigger of zonulin release is small intestinal exposure to gluten. Wheat ingestion can cause symptoms of Atopic dermatitis.[4]

Possible causes of elevated levels:

• Untreated inflammatory bowel disease (IBD).
• Disruption of the microbiota (dysbiosis) or a reaction to gluten or diet.
• Obesity and type 2 diabetes are conditions characterized by chronic inflammation and increased intestinal permeability in human studies, and may also be associated in dogs. [5]

Treatments:

• Decrease intestinal inflammation.[1]
• Supplementation with probiotics and/or prebiotics
  • Probiotic therapy was associated with upregulated (P< 0.05) expression of TJPs E-cadherin, occludin, and zonulin versus standard therapy.[4]
    • As compared with a standard diet, dogs with IBD fed probiotic had increased numbers of cells expressing E-cadherin, occludin, and zonulin tight junction proteins which suggests that the probiotic may have beneficial effects on mucosal homeostasis.[4]
  • Manipulation of the canine intestinal microbiota has been utilized for modifying atopy.
• Consider a therapeutic meal plan, such as a prescription diet dog food.
• Minimizing anxiety and stress.
• Antimicrobial therapy.
• Correction and prevention of low stomach acid.
• Several autoimmune, inflammatory, and neoplastic diseases have been associated with high levels.
  • Celiac disease, type 1 diabetes, juvenile nonalcoholic fatty liver disease, and may be associated with multiple sclerosis, rheumatoid arthritis, asthma, and inflammatory bowel disease.
• Fecal microbiota transplantation (FMT) has been proposed for significant GI issues.[2]

ANTIGLIADIN IGA

What is it:
Gluten can be an excellent source of protein for many dogs. As with people for some dogs they may develop antigliadin antibodies to gliadin, a component of gluten. High level of antigliadin IgA is sometimes referred to as gluten sensitivity. One assessment is via fecal antigliadin IgA assessment. Though as in people it is not thought to be indicative of celiac disease, it may identify a specific immune reaction to gluten. This is more likely to be an issue in dogs with GI issues such as diarrhea or skin reactions.

“Some breeds, such as Cocker Spaniels, Labrador Retrievers, Golden Retrievers, German Shepherd Dogs, Poodles, and Chinese Shar-Pei, may be at greater risk for food allergies, though they can appear in any breed.” – American Kennel Club[6]

Antigliadin IgA may identify an immune response to gluten containing pet foods and can monitor level of gluten exposure. Gliadin is a component of gluten. Increased Antigliadin IgA has been associated with increased Zonulin levels. Removing gluten can reduce antigliadin levels. Often gluten reactions decrease once the gut is repaired.

Treatments:

• Avoiding gluten will decrease antigliadin levels.
• Consider addressing overall gut health, gut permeability or inflammation.
  • Probiotics, improved diet, anti-inflammatory products.

References:

1. Catherine Barnette, D. Leaky Gut Syndrome in Dogs. [cited 2022; Available from: https://vcahospitals.com/know-your-pet/leaky-gut-syndrome-in-dogs.
2. Craig, J.M., Atopic dermatitis and the intestinal microbiota in humans and dogs. Vet Med Sci, 2016. 2(2): p. 95-105.
3. Rossi, G., et al., Clinicopathological and Fecal Proteome Evaluations in 16 Dogs Presenting Chronic Diarrhea Associated with Lymphangiectasia. Vet Sci, 2021. 8(10).
4. White, R., et al., Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. Gut Microbes, 2017. 8(5): p. 451-466.
5. Ohlsson, B., et al., Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents. Biomed Rep, 2017. 6(4): p. 411-422.
6. Kane, G. Dog Allergy Symptoms: What’s Causing Them and How to Treat it. 2013; Available from: https://www.akc.org/expert-advice/health/food-allergies-dog-scratching-licking/.