Study of Gut Microbiota Diversity in Children Aged 1-3 Years on Prolonged Antibiotic Prophylaxis for Grade 3 or Higher Vesicoureteral Reflux Compared With 2 Age-matched Control Groups (PROPHYBIOTA)

Urinary tract infections are very common in pediatrics. Urinary antibiotic prophylaxis is commonly used in children with malformative uropathies. Long-term, low-dose antibiotic prophylaxis with trimethoprim-sulfamethoxazole has been associated with a decrease in the number of urinary tract infections in susceptible children, but not systematically with a decrease in the risk of renal scarring (depending of uropathy stage).

Long-term antibiotic prophylaxis has implications for the acquisition of antibiotic resistance. A child receiving antibiotic prophylaxis for urinary tract infection is around 6 times more likely to develop a multidrug-resistant infection. In the general population, the microbiota of children treated with curative antibiotics is less diverse in terms of species and strains. In addition, short-term compositional changes are observed between consecutive samples of children treated with antibiotics.

The gut microbiota modulates the immune system, in particular via metabolites (SCFA, polysaccharide A) produced by bacteria that modify the expansion and function of regulatory T-cells. The disturbances of the intestinal microbiota play a role in the medium and long term on the acquisition of pathologies, such as atopy.

The study authors wish to describe the intestinal microbiota of children with vesico-ureteral reflux treated long-term with trimethoprim-sulfamethoxazole and compared it those not receiving antibiotic prophylaxis and to healthy children.

Study Overview

• Status: Recruiting
• Conditions: Vesicoureteral Reflux 3
• Intervention / Treatment: Other: Stool sampling

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Anne Filleron; Phone Number: 04.66.68.32.86; Email: anne.filleron@chu-nimes.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • CHU de Montpellier
    • Contact: Denis Morin; Phone Number: 04.67.33.64.28; Email: d-morin@chu-montpellier.fr
    • Principal Investigator: Denis Morin
    • Sub-Investigator: Nicolas Kalfa
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Sub-Investigator: Tu Anh Tran
    • Sub-Investigator: Catherine Dunyach-Remy
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr
    • Sub-Investigator: Jean-Philippe Lavigne
    • Principal Investigator: Anne Filleron
    • Sub-Investigator: Guillaume Germier
    • Sub-Investigator: Massimo Di Maio
    • Sub-Investigator: Edith Sabatier
    • Sub-Investigator: Margot Ollivier
    • Sub-Investigator: Sarah Garnier
    • Sub-Investigator: Viviane Wittmeyer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

For the purpose of the study three groups of children will be constituted:

Children aged 1 to 3 years with vesico ureteral reflux of grade 3 or higher, under antibiotic prophylaxis; Children aged 1 to 3 years with uropathy, without antibiotic prophylaxis; Controls: Healthy children aged 1 to 3 years.

Description

Inclusion Criteria:

• The patient must be a member or beneficiary of a health insurance plan
• Patient with no objection to participation in the study from the parent or guardian

• Child with a diversified diet.

  o Specific inclusion criteria for group 1 (cases):

• Child with grade 3 or higher vesicoureteral reflux.

• Child on trimethoprim-sulfamethoxazole therapy for at least 5 months.

  o Specific inclusion criteria for group 2 (controls):

• Child with uropathy and without long-term trimethoprim-sulfamethoxazole treatment.

  o Specific inclusion criteria for group 3 (healthy controls):

• Child without uropathy or long-term trimethoprim-sulfamethoxazole treatment.

Exclusion Criteria:

• Chronic digestive pathology
• Acute gastroenteritis or infectious colitis within last 15 days.
• Curative antibiotic therapy taken less than one month ago.
• Chronic inflammatory bowel disease or other localizations
• Congenital or acquired immune deficiency (current treatment with methotrexate, biotherapies, immunosuppressants)
• Patient participating in a category 1 trial likely to modify the intestinal microbiota.
• Patient in an exclusion period determined by another study.
• Patient under court protection, guardianship or curatorship.
• Patient for whom it is impossible to give informed information to person with parental authority.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Children aged 1 to 3 years with vesico ureteral reflux of grade 3 or higher, under antibiotic prophylaxis	Other: Stool sampling; Stool sample taken at home 24 hours before hospital visit
Controls; Children aged 1 to 3 years with uropathy, without antibiotic prophylaxis	Other: Stool sampling; Stool sample taken at home 24 hours before hospital visit
Healthy Controls; Healthy children aged 1 to 3 years.	Other: Stool sampling; Stool sample taken at home 24 hours before hospital visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
α-diversity of the gut microbiota between groups	N index of a stool sample measured by the Shannon index (H^') which incorporates the total number of different Operational Taxonomic Units and the relative proportions of these Operational Taxonomic Units.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The β-diversity of the gut microbiota between groups	Operational Taxonomic Units measured by Bray Curtis Index	Day 0
The number of bacterial genera present in the gut microbiota between groups	Relative abundance Operational Taxonomic Units present	Day 0
The prevalence of multi-resistant bacteria	% of isolated bacteria producing extended spectrum betalactamase, carbapenemase-producing Enterococcus faecium and glycopeptide-resistant Enterococcus faecium and bacteria resistant to trimethoprim-sulfamethoxazole	Day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Anne Filleron, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Microbiota; Antibiotic prophylaxis
• Additional Relevant MeSH Terms: Digestive System Diseases; Urologic Diseases; Urinary Bladder Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Gastroesophageal Reflux; Vesico-Ureteral Reflux
• Other Study ID Numbers: NIMAO/2021-2/AF-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No