Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity.

NCT ID: NCT06884241

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-10
• Study Completion Date: 2025-01-10

Brief Summary

The aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate the effects of probiotics on symptoms and gut microbiota composition following gluten reintroduction.

The study included adults diagnosed with NCWS. Participants received a 6-week intervention with either probiotics or a placebo. For the first 4 weeks, all participants followed a gluten-free, low-FODMAP diet, after which gluten was reintroduced.

Gastrointestinal symptoms (using the modified Gastrointestinal Symptom Rating Scale (GSRS)) and fecal samples were collected at baseline (T0), after 4 weeks (T1), and after 6 weeks (T2). Gut microbiome composition was assessed through whole-shotgun metagenomic sequencing and fecal volatile organic compounds (VOCs) were analyzed using gas chromatography-mass spectrometry (GC-MS).

Detailed Description

Non-Celiac Gluten Sensitivity (NCGS), or Non-Celiac Wheat Sensitivity (NCWS), is a condition characterized by the onset of gastrointestinal and systemic symptoms following the consumption of gluten-containing foods, without the presence of celiac disease or wheat allergy.

The aim of the present randomized, double-blind controlled trial is to explore probiotics as a potential therapeutic option to alleviate symptoms and improve gut microbiome composition.

Participants Eligible participants were adults aged 18 or older with NCGWS, confirmed by a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test. Those with conditions like Crohn's disease, wheat allergy, IBS, gastrointestinal issues, infections, psychiatric disorders, or those on specific medications, as well as pregnant or breastfeeding individuals, were excluded.

Intervention Participants were randomized to receive for 6 weeks 2 sachets of probiotics (Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106) (experimental arm) or 2 sachets of placebo (control arm). All participants a gluten-free and low FODMAPs diet. After 4 weeks, foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten).

The investigators and the participants were blinded to the procedure. The probiotic and placebo sachets were identical and in identical packaging.

Measurements

At baseline (T0), after 4 weeks (T1, end of gluten-free diet), and after 6 weeks (T2, study-end), participants were submitted to the following measurements:

• modified GSRS questionnaire
• collection of a fecal sample for gut microbiota determination. At T1 and T2, volatile organic fractions of stool samples were assessed and whole shotgun metagenomics were performed.

Conditions

Gluten Sensitivity; Wheat Sensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention arm

Participants in this arm received a supplementation of probiotics for 6 weeks.

Group Type: EXPERIMENTAL

Probiotic supplementation

Intervention Type: DIETARY_SUPPLEMENT

The intervention consists of a 6-week supplementation with a specific combination of probiotics: Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106. All participants were given a gluten-free, low FODMAPs diet. After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained

Control arm

Participants in this arm received placebo for 6 weeks. The placebo were identical in size, shape, color, and taste to the probiotic.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The participants received placebo for 6 weeks. Placebo was identical in appearance, texture, taste, and packaging to the probiotic treatment. All participants were given a gluten-free, low FODMAPs diet.

After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained

Interventions

Probiotic supplementation

The intervention consists of a 6-week supplementation with a specific combination of probiotics: Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106. All participants were given a gluten-free, low FODMAPs diet. After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained

Intervention Type: DIETARY_SUPPLEMENT

Placebo

The participants received placebo for 6 weeks. Placebo was identical in appearance, texture, taste, and packaging to the probiotic treatment. All participants were given a gluten-free, low FODMAPs diet.

After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• age≥18 years
• NCGWS demonstrated by the following self-reported conditions i) intestinal and extra intestinal symptoms associated within hours or days after the ingestion of gluten-containing food, ii) a clear benefit while on a gluten-free diet, iii) relapse of symptoms with the ingestion of gluten-containing foods, iv) a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test, as previously described.

Exclusion Criteria

• presence of Crohn disease (CD), wheat allergy (WA), irritable bowel syndrome (IBS), and other gastrointestinal diseases, H. Pylori infection, lactose intolerance, history of gastrointestinal surgery, liver/pancreatic diseases, active or recent infection diseases, known psychiatric diseases, any systemic diseases
• pregnancy or breastfeeding
• active use of antibiotics, pre-probiotics, immunosuppressive drugs, non-steroidal anti-inflammatory drugs, or corticosteroids,
• inability to give written informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Turin, Italy

OTHER

Sponsor Role: lead

Responsible Party

Simona Bo

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simona Bo, Associate Professor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Torino

Ilario Ferrocino, Professor

Role: STUDY_DIRECTOR

University of Turin, Italy

Locations

AOU Città della Salute e della Scienza di Torino, University of Torino

Torino, , Italy

Countries

Italy

Other Identifiers

GLUTEN_2024

Identifier Type: -

Identifier Source: org_study_id