Restoration of the Gut Microbiome After Cesarean Section

Phase 1

Not yet recruiting

• Conditions: Microbial Colonization
• Interventions: Biological: Microbiome restoration - FMT; Other: Vaginal birth, untreated control; Biological: Microbiome restoration - FVT; Biological: Placebo

• Registration Number: NCT06264219
• Lead Sponsor: Professor Klaus Bønnelykke

Brief Summary

This study aims to develop a therapy for restoring the gut microbiome in infants born via CS. We will conduct a randomized, placebo-controlled feasibility trial to assess the ability of microbiome restoration by FMT and FVT in infants born by cesarean section.

Detailed Description

When a child is born vaginally, the passage through the birth canal provides the first and very important bacterial colonization. As the child ages, various environmental exposures, such as dietary changes and the presence of older siblings in the home, facilitate a natural maturation of the child's gut microbiome, providing a vast and continuous stimulation of the child's developing immune system. However, factors such as mode of delivery and intrapartum antibiotics can perturb this natural developmental process and cause long-term microbial derangements. The prevalence of cesarean section (CS) birth has increased globally in recent decades, and with it, antibiotic treatment to prevent perinatal infection. Similar patterns have occurred for the prevalence of chronic childhood disease, particularly asthma, with an estimated 300 million asthmatic cases worldwide.

We hypothesize that early intervention with mother-to-infant FMT can restore a CS-perturbed microbiome to a normal microbial trajectory. We also hypothesize that seeding the virome fraction (FVT) will cause the neonate's microbiome to resemble the mother's since the transferred phages are enriched and preserved in the intestinal mucus layer, thereby providing the recipient with selective antimicrobial protection while allowing species resembling the mother's own to establish during subsequent bacterial transmission.

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-12
• Study First Submitted QC: 2024-02-12
• Last Update Submitted: 2024-02-12
• Study First Posted: 2024-02-16
• Last Update Posted: 2024-02-16
• Study Start: 2024-03-01
• Primary Completion: 2025-11-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 80

Inclusion Criteria

• Gestational age < week 38+0 days
• Proficient in spoken/written Danish
• Single pregnancy (no twins or triplets)
• Pre-pregnancy BMI between 18.5 and 35 kg/m2
• No chronic intestinal, endocrine, cardiac, or kidney disorders
• No known gestational complications (gestational diabetes, preeclampsia, gestational hypothyroidism)
• No regular use of prescription medication or any drugs that, in the research team's opinion, may interfere with the study's results.
• Willingness to abstain from giving the child products with probiotics (fermented dairy like yogurt or A38 are allowed).

Exclusion Criteria

Maternal:

• Use of antibiotics within one month of stool donation
• Acute gastroenteritis within one month of stool donation
• Use of antibiotics within one month of birth
• Time since last travel abroad relative to data of fecal donation according to the requirements for blood donations ("Regler for tappepauser" - blooddonor.dk)
• Positive test results for pathogens during donor material screening.
• Antibiotic treatment at birth (vaginal births only)
• Spontaneous onset of labor or emergency cesarean section before scheduled cesarean section.

Infant:

• Instances of major birth defects or intrauterine growth retardation (IUGR)
• Infants requiring pediatric support at the time of transplant administration

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FMT (Fecal microbiota transplantation)	Microbiome restoration - FMT	Mother-to-infant fecal microbiota transplantation
Vaginal control group	Vaginal birth, untreated control	Non-randomized control group used for secondary outcomes comparisons.
FVT (Fecal virome transplantation)	Microbiome restoration - FVT	Mother-to-infant fecal virome transplantation
Placebo	Placebo	Inactive solution buffer placebo

Primary Outcome Measures

Name	Time	Method
Microbial compositional differences to placebo-treated infants	During the first year of life	Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

Secondary Outcome Measures

Name	Time	Method
Microbial compositional resemblance to vaginally-born infants	During the first year of life	Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

Trial Locations

Locations (2)

Copsac, DBAC; 🇩🇰 Gentofte, Copenhagen, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark