Intestinal Microbiota After PPI Treatment (PPI)

June 25, 2025 updated by: Ruggiero Francavilla, University of Bari

Evaluation of the Intestinal Microbiota in Pediatric Patients Treated With Proton Pump Inhibitors: A Prospective Longitudinal Study

This clinical study aims to investigate the effects of short-term treatment with proton pump inhibitors (PPIs) on the gut microbiota of pediatric patients. PPIs are among the most frequently prescribed medications in children and adolescents for the management of acid-related disorders, such as gastroesophageal reflux disease (GERD). However, emerging evidence suggests that these medications may have unintended consequences on the delicate ecosystem of beneficial microorganisms residing in the human gastrointestinal tract.

The intestinal microbiota plays a pivotal role in modulating immune responses, supporting nutrient metabolism, and maintaining the integrity of the gut barrier. Disruption of this microbial balance-known as dysbiosis-has been associated with several health conditions, including infections, allergies, obesity, and chronic inflammation. In adults, long-term PPI use has been linked to microbiota alterations, but data in the pediatric population remain limited and inconclusive.

To address this gap, our prospective longitudinal study will recruit pediatric patients prescribed PPI therapy for clinical indications. Stool samples will be collected at four time points: prior to PPI administration, during treatment, and at two follow-up stages post-cessation. Using 16S rRNA gene sequencing, we will profile changes in microbial diversity and abundance over time.

The results will offer insight into whether short-term PPI exposure in children leads to significant, lasting changes in gut microbiota composition or diversity. Such information may ultimately inform prescribing practices, support personalized therapeutic strategies, and help mitigate potential risks associated with microbiota disruption during childhood-a critical period for microbial and immune system development.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bari, Italy, 70100
        • Pediatria Trambusti

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Population with GERD

Description

Inclusion Criteria:

  • Male or female children and adolescents aged between 6 months and 17 years at the time of enrollment.
  • Clinical indication for proton pump inhibitor therapy, including but not limited to gastroesophageal reflux disease, esophagitis, or functional dyspepsia.
  • Willingness and ability of the child and their caregivers to comply with all study procedures, including collection of fecal samples at scheduled time points.
  • Written informed consent obtained from a parent or legal guardian; assent obtained from the child, when age-appropriate, in accordance with local regulations and ethical standards.

Exclusion Criteria:

  • Use of systemic antibiotics, antifungals, or probiotics within 30 days prior to the start of the study or during the observation period.
  • Incomplete or improperly handled stool sample collection, or failure to adhere to protocol-defined sampling windows.
  • Known diagnosis of primary immunodeficiency, inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or celiac disease.
  • Any condition that, in the opinion of the investigator, may interfere with the integrity of the study or pose additional risks to the participant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PPI
Other: study of microbiota
  • Drug: Esomeprazole, a proton pump inhibitor commonly used in pediatric gastroenterology.
  • Administration: Oral, once daily, 30 minutes before meals.
  • Dosage: Personalized dosing according to body weight, with an average of approximately 0.6 mg/kg/day.
  • Treatment duration: Minimum 45 days, maximum 60 days.
  • Comparator: None. This is a within-subject design; each participant serves as their own control with baseline samples (t0) compared to follow-up (t1-t2).
  • Monitoring: Adherence to therapy and sample collection timeline will be verified during scheduled clinical follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in microbiota
Time Frame: 60 days from baseline
  • Definition: Change in the relative abundance of key bacterial families (Streptococcaceae, Ruminococcaceae, Clostridiales, etc.) from t0 to t1.
  • Methodology: High-throughput 16S rRNA gene sequencing (regions V3-V4) using the Illumina MiSeq platform; taxonomic assignment via the SILVA reference database.
  • Justification: These bacterial families have been previously associated with dysbiosis and PPI-related shifts in microbial composition.
60 days from baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbial diversity
Time Frame: 60 days from baseline.
  • Alpha-diversity: Within-sample microbial diversity measured by Shannon's entropy and Chao1 richness estimator.
  • Beta-diversity: Between-sample differences using Bray-Curtis dissimilarity; visualized via principal coordinates analysis (PCoA).
  • Differential abundance: Identification of statistically enriched or depleted taxa using LEfSe (Linear Discriminant Analysis Effect Size).
  • Clinical correlation: Incidence of gastrointestinal (e.g., diarrhea, abdominal pain) and respiratory symptoms (e.g., cough, wheezing) reported during or after therapy.
60 days from baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bari

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 6, 2025

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

June 16, 2025

First Submitted That Met QC Criteria

June 16, 2025

First Posted (Actual)

June 25, 2025

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 25, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PPI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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