Clinical trial NCT05798689: Use of a Selected Mixture of Probiotic Strains for Degrading Gluten During Digestion
Official title: Novel Probiotic Preparation With Gluten Degrading Activity and Gut Microbiota Modulating Effect
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Probiotics
Keywords: Gluten
Gut microbiome
Celiac disease
Lead sponsor: Free University of Bozen-Bolzano
Sponsor class: OTHER
Collaborators: name: Evonik Operations GmbH, Germany
First posted: 2023-04-04
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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

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)

Primary outcomes:
measure: Hydrolyzed gluten amount in feces by competitive Elisa R5 antibody (gluten ppm)
timeFrame: 6 months
measure: Gut microbiome
timeFrame: 7 months
measure: Volatile compounds determination by GC-MS using SPME extraction
timeFrame: 6 months
measure: Short chain fatty acids determination by GC-MS using SPME extraction
timeFrame: 6 months
measure: Persistence and colonization ability of probiotic preparation by quantitative PCR (copy numbers)
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bolzano
country: Italy
facility: Free University of Bolzano-Bozen
Study officials:
affiliation: Free University of Bolzano-Bozen
name: Olga Nikoloudaki, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.