Digestion of Gluten in the Presence of Enzymes

Study Overview
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Brief Summary
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This study evaluates the impact of two dietary supplements (Glutalytic® and DE111®) and of oatmeal properties on the digestion of gluten and starch and on the glycemic response.

Detailed Description
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RATIONALE Two important factors can influence the proportions of gluten and starch that resist digestion: (1) enzyme availability and specificity and (2) the structural properties of the food. Glutalytic®, is a dietary supplement based on an enzyme preparation which effectively degrades gluten in vitro (Healey, Hall et al. unpublished). As it has also been found that the rate of wheat protein digestion can be increased in the presence of amylases (Smith, Pan et al. 2015), Glutalytic ® is also enriched with amylase to aid in starch digestion. The structural properties of food are influenced by numerous factors including meal preparation practices. Two common practices that can influence nutrient availability differently are heating vs. refrigerating (e.g. oat porridge vs. soaked and refrigerated oats). Bacillus subtilis DE111® can produce and secrete many enzymes, including proteases, which, if secreted into the environment of the digestive tract, could support digestion and, in particular, the digestion of gluten. However, it is not clear whether diet supplementation with DE111 is a physiologically viable approach in terms of probiotic survival in the gastrointestinal tract. PURPOSE The aims of this study are to better understand the impact of each of these factors and whether supplementation with probiotic spores is a viable option.

Official Title
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GlutDigest - Enzymes-assisted Gluten Digestion

Conditions
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Main Focus: Gluten and Starch Digestibility

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Glutalytic®
* Dietary Supplement: DE111®
* Other: Meal A
* Other: Meal B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has given written informed consent Subject has an ileostomy stable for at least 3 months post-operative and shows normal stoma functions Subject is otherwise healthy Subject is available to participate in the study sessions on the proposed dates Exclusion Criteria: Subject has coeliac disease or allergy to wheat products and/or any other ingredients in the test meal and standard meals Case of obstruction of the stoma in the past 3 months Body mass index < 18 kg/m2 or > 30 kg/m2. Diagnosed mouth, throat or active gastrointestinal pathology (other than ileostomy) that may affect normal ingestion and digestion of food. History of pancreatic disease Subject is immunocompromised (HIV positive, transplant patient, on antirejection medications, on a steroid for >30 days, or chemotherapy or radiotherapy within the last year) Subject has Type 1 or Type 2 diabetes mellitus. Subject has a history of bariatric surgery. Subject has a history of drug and/or alcohol abuse at the time of enrolment Subject is currently participating in another study, or plans to participate in another study during the study period Women of child-bearing potential who do not use an acceptable method of contraception Pregnant or nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Meal A + Placebo<br>350 mg Placebo capsule, taken by mouth, once, with Meal A | Dietary Supplement: Placebo<br>* Maltodextrin capsule manufactured to mimic the Glutalytic® and DE111® capsules<br>Other: Meal A<br>* Oatmeal porridge - serving of cooked oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL<br>|
| Experimental: Meal A + Glutalytic®<br>350 mg Glutalytic® capsule, taken by mouth, once, with Meal A | Dietary Supplement: Glutalytic®<br>* 1 capsule containing 350 mg of Glutalyltic®<br>Other: Meal A<br>* Oatmeal porridge - serving of cooked oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL<br>|
| Experimental: Meal A + DE111®<br>350 mg DE111® capsule, taken by mouth, once, with Meal A | Dietary Supplement: DE111®<br>* 1 capsule containing Bacillus subtilis DE111<br>Other: Meal A<br>* Oatmeal porridge - serving of cooked oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL<br>|
| Experimental: Meal B + Placebo<br>350 mg Placebo capsule, taken by mouth, once, with Meal B | Dietary Supplement: Placebo<br>* Maltodextrin capsule manufactured to mimic the Glutalytic® and DE111® capsules<br>Other: Meal B<br>* Refrigerated oatmeal - serving of refrigerated oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undigested wheat protein | Difference between the mean concentration of undigested wheat protein in ileal effluent samples. | 9-hour period after the test meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vegetative DE111 cells | Mean concentration of DE111® cells recovered in the ileal effluent in the vegetative state. | 9-hour period after the test meal | 
| Glycemic response | Difference between the mean area under the glucose concentration (measured in the interstitial fluid) curves following each treatment | At baseline, and at different time-points during 9 hours after after consuming the test meal. | 
| Undigested starch | Difference between the mean concentration of undigested starch in ileal effluent samples. | At baseline and once every hour in the 9-hour period after consumption of the test meal. | 
| Undigested food particles | Pictures of undigested foods particles and microscopy will be combined for a combined assessment of macro- and micro- structural characteristics of the food particles recovered in ileal effluent samples. | 9-hour period after the test meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gluten, Starch, Digestive enzymes, Probiotics