Restoration of the Gut Microbiome After Cesarean Section (RestoreGut)

Professor Klaus Bønnelykke

Status and phase: Enrolling; Phase 1

Conditions: Microbial Colonization

Treatments: Other: Vaginal birth, untreated control; Biological: Microbiome restoration - FMT; Biological: Placebo; Biological: Microbiome restoration - FVT

Study type: Interventional

Funder types: Other

Identifiers

NCT06264219

H-24002284

Details and patient eligibility

About

This study aims to develop a therapy for restoring the gut microbiome in infants born via CS. The Study 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.

Full 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.

The hypothesis is that early intervention with mother-to-infant FMT can restore a CS-perturbed microbiome to a normal microbial trajectory. Another hypothesis is 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.

Enrollment: 80 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 4 patient groups, including a placebo group

FMT (Fecal microbiota transplantation)

Active Comparator group

Description:

Mother-to-infant fecal microbiota transplantation

Treatment:

Biological: Microbiome restoration - FMT

FVT (Fecal virome transplantation)

Active Comparator group

Description:

Mother-to-infant fecal virome transplantation

Treatment:

Biological: Microbiome restoration - FVT

Placebo

Placebo Comparator group

Description:

Inactive solution buffer placebo

Treatment:

Biological: Placebo

Vaginal control group

Other group

Description:

Non-randomized control group used for secondary outcomes comparisons.

Treatment:

Other: Vaginal birth, untreated control