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

Not Applicable

Completed

• Conditions: Gluten Sensitivity; Wheat Sensitivity

• Registration Number: NCT06884241
• Lead Sponsor: University of Turin, Italy

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.

Study Timeline

• Study Start: 2018-09-10
• Primary Completion: 2024-12-03
• Study Completion: 2025-01-10
• Status Verified: 2025-03
• Study First Submitted: 2025-03-07
• Study First Submitted QC: 2025-03-12
• Last Update Submitted: 2025-03-12
• Study First Posted: 2025-03-19
• Last Update Posted: 2025-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Symptoms Following Gluten Reintroduction	Symptoms were assessed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).	The primary outcome was evaluating between-group differences in symptoms reported by participants after gluten reintroduction, as measured by the modified Gastrointestinal Symptom Rating Scale (GSRS), according to the Salerno Experts criteria. Participants were defined as "tolerant" to the gluten-containing diet if their total GSRS scores did not change or reduced 2 weeks after the gluten introduction (T2)

Secondary Outcome Measures

Name	Time	Method
Gut microbiome composition after probiotic supplementation	Gut microbiome was analyzed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).	The assessment of gut microbiome composition after probiotic supplementation. Gut microbiome composition was assessed through whole-shotgun metagenomic sequencing.
Fecal volatilome after probiotic supplementation	Volatilome was analyzed at baseline and after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).	The assessment of volatilome after probiotic supplementation by gas chromatography-mass spectrometry

Trial Locations

Locations (1)

AOU Città della Salute e della Scienza di Torino, University of Torino; 🇮🇹 Torino, Italy