Use of a Selected Mixture of Probiotic Strains for Degrading Gluten During Digestion

NCT ID: NCT05798689

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2021-05-31

Brief Summary

Gluten intake spreads worldwide, being the major food protein consumed in the Western diets (up to 20 g gluten/d). But gluten has unique and unusual features. It resists the complete luminal digestion by gastric, pancreatic and intestinal brush border enzymes, and is susceptible to post-translational modification (deamidation) by mucosal transglutaminases. Apart from partial digestion, gluten per se has a negative impact on a consistent part of the worldwide population, which mainly results in the manifestations of celiac disease (CD) or other gluten-related disorders. This study will enable to test in vivo a novel multi-species probiotic that in vitro has proven to degrade gluten to non-immunotoxic peptides.

Detailed Description

Hypothesis and Significance:

The project intends to confirm whether the novel multi-species probiotic preparation has the ability to degrade gluten upon digestion at increasing dosages (from 50mg/d up to 10g/d). Further we aim to evaluate the efficiency of the probiotic to persist and colonize the human gut as well as its ability to modulate the human gut microbiome.

Since this is a phase 1 trial, healthy participants will be recruited to avoid any triggers of CD symptoms. Participants will undergo gluten free diet for 10 days to eliminate any traces of gluten from their feces and will be provided probiotic/placebo capsules as long as specific amounts of gluten to be ingested with their meal. Faecal samples will be collected at the end of each period that increasing gluten amounts were ingested. Residual gluten amounts in feces will be evaluated and the fecal microbiome will be studied by 16S metabarcoding analysis. Fecal metabolome will be also assessed as long as the persistence and colonisation ability of the probiotic preparation by qPCR.

Specific Aim 1:

Evaluate the gluten depredating efficiency of the probiotic by ELISA

Specific Aim 2:

Investigate the gut microbiome alterations between the intervention groups and possible modulation

Specific Aim 2:

Investigate the fecal metabolome (Volatiles and short chain fatty acids) between intervention groups

Specific Aim 2:

Monitor the persistence and colonization ability of the probiotic preparation by qPCR

Conditions

Probiotics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: TRIPLE

Study Groups

PR

Fifty healthy volunteers were randomly allocated in the probiotic arm. To eliminate residual traces of gluten and similar proteins from the faecal material, both groups underwent a gluten-free diet (GFD) from day-1 to day-10. After 10 days, gluten administration started. The increasing administration plan was as follows: 50 mg/day for 4 days; 1 g/day for subsequent 4 days; 3 g/day for subsequent 4 days; and 10 g/day (in this case, reintroducing an equivalent amount of wheat-based bread - 4 slices) for subsequent 20 days. At this stage (10 + 4 + 4 + 4 + 10 days = total of 32 days), the administration of the probiotic preparation was interrupted, with a period of 10 days of wash-out.

Group Type: ACTIVE_COMPARATOR

Probiotic administration and gluten

Intervention Type: COMBINATION_PRODUCT

Probiotic preparation including multi-species strains of Lactobacillus and Bacillus. The probiotic was administered at baseline and interrupted after 32 days. At the same time the other arm received placebo. Gluten was provided after 10 days of gluten free diet in increasing amounts

PL

Twenty healthy volunteers were randomly allocated in the placebo.To eliminate residual traces of gluten and similar proteins from the faecal material, both groups underwent a gluten-free diet (GFD) from day-1 to day-10. After 10 days, gluten administration started. The increasing administration plan was as follows: 50 mg/day for 4 days; 1 g/day for subsequent 4 days; 3 g/day for subsequent 4 days; and 10 g/day (in this case, reintroducing an equivalent amount of wheat-based bread - 4 slices) for subsequent 20 days. At this stage (10 + 4 + 4 + 4 + 10 days = total of 32 days), the administration of placebo preparation was interrupted, with a period of 10 days of wash-out.

Group Type: PLACEBO_COMPARATOR

Placebo administration and gluten

Intervention Type: COMBINATION_PRODUCT

The placebo was administered at baseline and interrupted after 32 days. At the same time the other arm received probiotic. Gluten was provided after 10 days of gluten free diet in increasing amounts

Interventions

Probiotic administration and gluten

Probiotic preparation including multi-species strains of Lactobacillus and Bacillus. The probiotic was administered at baseline and interrupted after 32 days. At the same time the other arm received placebo. Gluten was provided after 10 days of gluten free diet in increasing amounts

Intervention Type: COMBINATION_PRODUCT

Placebo administration and gluten

The placebo was administered at baseline and interrupted after 32 days. At the same time the other arm received probiotic. Gluten was provided after 10 days of gluten free diet in increasing amounts

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• healthy individuals;
• adherent to Mediterranean diet

Exclusion Criteria

• known medical disease;
• known digestive disease symptoms;
• known family history of celiac disease (CD);
• wheat allergy;
• and use of prescription medications (including antibiotics or probiotics in the previous 2 months)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Evonik Operations GmbH, Germany

UNKNOWN

Sponsor Role: collaborator

Free University of Bozen-Bolzano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olga Nikoloudaki, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Free University of Bolzano-Bozen

Locations

Free University of Bolzano-Bozen

Bolzano, , Italy

Countries

Italy

References

De Angelis M, Siragusa S, Vacca M, Di Cagno R, Cristofori F, Schwarm M, Pelzer S, Flugel M, Speckmann B, Francavilla R, Gobbetti M. Selection of Gut-Resistant Bacteria and Construction of Microbial Consortia for Improving Gluten Digestion under Simulated Gastrointestinal Conditions. Nutrients. 2021 Mar 19;13(3):992. doi: 10.3390/nu13030992.

Reference Type: BACKGROUND

PMID: 33808622 (View on PubMed)

Other Identifiers

GlutProbiotic

Identifier Type: -

Identifier Source: org_study_id