Clinical trial NCT06884241: Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity.
Official title: Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity. A Randomized Controlled Double-blind Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gluten Sensitivity
Wheat Sensitivity
Keywords: gluten sensitivity
wheat sensitivity
probiotics
microbiome
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2025-03-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Symptoms Following Gluten Reintroduction
timeFrame: Symptoms were assessed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Secondary outcomes:
measure: Gut microbiome composition after probiotic supplementation
timeFrame: Gut microbiome was analyzed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
measure: Fecal volatilome after probiotic supplementation
timeFrame: Volatilome was analyzed at baseline and after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Other outcomes:
Locations:
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino, University of Torino
Study officials:
affiliation: University of Torino
name: Simona Bo, Associate Professor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turin, Italy
name: Ilario Ferrocino, Professor
role: STUDY_DIRECTOR
References: