Intestinal Microbiota After PPI Treatment

NCT07036627 | Not Yet Recruiting

• 1 other identifier: PPI
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Proton Pump Inhibitors; Human Gastrointestinal Tract; Gastroesophageal Reflux Disease

Keywords

PPI; GERD; microbiota; gastroesophageal reflux

Outcome Measures

Primary Outcomes (1)

• 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.

  60 days from baseline

Secondary Outcomes (1)

• Microbial diversity

  60 days from baseline.

Study Arms (1)

PPI

PPI

Other: study of microbiota

Interventions

study of microbiota OTHER

* 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.

PPI

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Population with GERD

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Bari: lead

Study Sites (1)

Pediatria Trambusti

Bari, Bari, 70100, Italy

Location

Related Publications (6)

• Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. 2018 Jun 4;172(6):e180315. doi: 10.1001/jamapediatrics.2018.0315. Epub 2018 Jun 4.

  PMID: 29610864 BACKGROUND

• Simakachorn L, Tanpowpong P, Chanprasertyothin S, Thongpradit S, Treepongkaruna S. Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors. Turk J Gastroenterol. 2021 Jan;32(1):70-75. doi: 10.5152/tjg.2020.20245.

  PMID: 33893768 BACKGROUND

• Raisanen L, Viljakainen H, Kolho KL. Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases. Front Pediatr. 2023 Mar 27;11:1157547. doi: 10.3389/fped.2023.1157547. eCollection 2023.

  PMID: 37051434 BACKGROUND

• Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020 Aug;109(8):1531-1538. doi: 10.1111/apa.15213. Epub 2020 Mar 18.

  PMID: 32027402 BACKGROUND

• Zhang YJ, Connearney S, Hester L, Du M, Catacora A, Akkara A, Wen A, Bry L, Alm EJ, Rosen R. Longitudinal Microbiome Changes in Children Exposed to Proton Pump Inhibitors. Clin Transl Gastroenterol. 2024 Sep 1;15(9):e1. doi: 10.14309/ctg.0000000000000703.

  PMID: 38624107 BACKGROUND

• Liu C, Bach TR, Farrell PM, Pavelec D, Antos NJ, Rock MJ, Asfour F, Howenstine M, Gaffin JM, Lai HJ. Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2024 Dec;79(6):1124-1133. doi: 10.1002/jpn3.12389. Epub 2024 Oct 28.

  PMID: 39465618 BACKGROUND

MeSH Terms

Conditions

Gastroesophageal Reflux

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Central Study Contacts

Ruggiero Francavilla, Prof

CONTACT

00390805592063; ruggiero.francavilla@uniba.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Ruggiero Francavilla

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: June 25, 2025
• Study Start: July 6, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: June 29, 2025

Record last verified: 2025-06

Locations

IT (1)