Intestinal Microbiota After PPI Treatment

N/ANot Yet RecruitingNCT07036627

University of Bari100 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

100

Conditions

Proton Pump Inhibitors Human Gastrointestinal Tract

Interventions

study of microbiotaOTHER

* 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.

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 17 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Changes in microbiota

* 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.

Time frame: 60 days from baseline

Secondary Outcomes

Microbial diversity

* 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.

Time frame: 60 days from baseline.