Dr. Ron’s Research Review – January 10, 2018

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This week’s research review focuses on sourdough wheat for celiac disease

Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. In this randomized, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. (Salden et al., 2015)
Fermentation of wheat flour with sourdough lactobacilli and fungal proteases decreases the concentration of gluten. This study evaluated the safety of daily administration of baked goods made from this hydrolyzed form of wheat flour to patients with CD.  Patients were randomly assigned to consumption of 200 g per day of natural flour baked goods (NFBG) (80,127 ppm gluten; n = 6), extensively hydrolyzed flour baked goods (S1BG) (2480 ppm residual gluten; n = 2), or fully hydrolyzed baked goods (S2BG) (8 ppm residual gluten; n = 5) for 60 days.  Two of the 6 patients who consumed NFBG discontinued the challenge because of symptoms; all had increased levels of anti-tissue transglutaminase (tTG) antibodies and small bowel deterioration. The 2 patients who ate the S1BG goods had no clinical complaints but developed subtotal atrophy. The 5 patients who ate the S2BG had no clinical complaints; their levels of anti-tTG antibodies did not increase, and their Marsh grades of small intestinal mucosa did not change.  A 60-day diet of baked goods made from hydrolyzed wheat flour, manufactured with sourdough lactobacilli and fungal proteases, was not toxic to patients with CD.  (Greco et al., 2011)
Eight patients with CD in remission were enrolled for the clinical challenge, and they daily consumed 200 g of sweet baked goods equivalent to 10 g of native gluten. Hematology, serology (total serum IgA, IgG and IgA antigluten, endomysial and tissue transglutaminase IgA antibodies), and intestinal permeability analyses were carried out over time. One patient interrupted the trial after 15 days and another after 30 days only due to difficulties in the compliance of the daily consumption. All of the other patients showed normal values of hematology, serology, and intestinal permeability during 60 days of challenge. This study showed that a wheat flour-fermented product, having gluten completely degraded, is not toxic for patients with CD. (Di Cagno et al., 2010)

Dr. Ron


 

Articles

Gluten-free sourdough wheat baked goods appear safe for young celiac patients: a pilot study.
            (Di Cagno et al., 2010) Download
OBJECTIVES:  This study was aimed at showing the safety, for young patients with celiac disease (CD), of sweet baked goods made of wheat flour, which was rendered gluten-free during sourdough fermentation. METHODS AND RESULTS:  As shown by R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay (ELISA), selected lactobacilli and fungal proteases, routinely used in bakeries, degraded gluten to <10 ppm during sourdough fermentation. The resulting flour was mainly a mixture of water-/salt-soluble low-size peptides and free amino acids. Gliadin and glutenin fractions extracted from the pepsin-trypsin (PT) digest of the fermented wheat flour induced the expression of interferon (IFN)-γ at the level comparable with the negative control. After fermentation, the wheat flour was spray dried and used for making sweet baked goods. Eight patients with CD in remission were enrolled for the clinical challenge, and they daily consumed 200 g of sweet baked goods equivalent to 10 g of native gluten. Hematology, serology (total serum IgA, IgG and IgA antigluten, endomysial and tissue transglutaminase IgA antibodies), and intestinal permeability analyses were carried out over time. One patient interrupted the trial after 15 days and another after 30 days only due to difficulties in the compliance of the daily consumption. All of the other patients showed normal values of hematology, serology, and intestinal permeability during 60 days of challenge. CONCLUSIONS:  This study showed that a wheat flour-fermented product, having gluten completely degraded, is not toxic for patients with CD. Nevertheless, these foods should not be recommended for patients with celiac disease until a formal trial has been done.

Safety for patients with celiac disease of baked goods made of wheat flour hydrolyzed during food processing.
            (Greco et al., 2011) Download
BACKGROUND & AIMS:  Celiac disease (CD) is characterized by an inflammatory response to wheat gluten, rye, and barley proteins. Fermentation of wheat flour with sourdough lactobacilli and fungal proteases decreases the concentration of gluten. We evaluated the safety of daily administration of baked goods made from this hydrolyzed form of wheat flour to patients with CD. METHODS:  Patients were randomly assigned to consumption of 200 g per day of natural flour baked goods (NFBG) (80,127 ppm gluten; n = 6), extensively hydrolyzed flour baked goods (S1BG) (2480 ppm residual gluten; n = 2), or fully hydrolyzed baked goods (S2BG) (8 ppm residual gluten; n = 5) for 60 days. RESULTS:  Two of the 6 patients who consumed NFBG discontinued the challenge because of symptoms; all had increased levels of anti-tissue transglutaminase (tTG) antibodies and small bowel deterioration. The 2 patients who ate the S1BG goods had no clinical complaints but developed subtotal atrophy. The 5 patients who ate the S2BG had no clinical complaints; their levels of anti-tTG antibodies did not increase, and their Marsh grades of small intestinal mucosa did not change. CONCLUSIONS:  A 60-day diet of baked goods made from hydrolyzed wheat flour, manufactured with sourdough lactobacilli and fungal proteases, was not toxic to patients with CD. A combined analysis of serologic, morphometric, and immunohistochemical parameters is the most accurate method to assess new therapies for this disorder.

Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.
            (Salden et al., 2015) Download
BACKGROUND:  Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM:  To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS:  In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS:  AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × min/mL; P = 0.001). CONCLUSIONS:  AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.


 

References

Di Cagno, R, et al. (2010), ‘Gluten-free sourdough wheat baked goods appear safe for young celiac patients: a pilot study.’, J Pediatr Gastroenterol Nutr, 51 (6), 777-83. PubMed: 20975578
Greco, L, et al. (2011), ‘Safety for patients with celiac disease of baked goods made of wheat flour hydrolyzed during food processing.’, Clin Gastroenterol Hepatol, 9 (1), 24-29. PubMed: 20951830
Salden, BN, et al. (2015), ‘Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.’, Aliment Pharmacol Ther, 42 (3), 273-85. PubMed: 26040627