Impact of Breast Milk miRNAs on the Infant Gut Microbiota

NCT ID: NCT06651216

Last Updated: 2024-10-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2027-05-31

Brief Summary

The first 1000 days of life are a critical period for future health. A healthy gut microbiota (GM) is essential for preventing both short-term and long-term health issues. Breast milk (BM) plays a key role in establishing the GM, as, unlike formula milk, it contains miRNAs that may interact with and modulate the microbiota.

Primary Objective: To study the effect of BM on the composition of fecal miRNAs in exclusively breastfed infants compared to those fed with formula milk at different times (D10, D30, D60, M6, M12).

Secondary Objectives:

Analyze the effect of BM miRNAs on infant fecal microbiota, taking environmental confounding factors into account.

Study the influence of BM microbiota on miRNA profiles in the milk. Examine the effect of BM microbiota on the infants' gut microbiota. Explore the links between BM miRNAs, infant gut microbiota, and intestinal inflammation.

Detailed Description

The first 1,000 days of life are a critical period that significantly contributes to the programming of an individual's health. It is increasingly evident that establishing a healthy gut microbiota (GM) plays an important role in preventing both short- and long-term health issues.

Among the factors influencing the establishment of the infant's gut microbiota, breast milk (BM) plays a fundamental role. Unlike formula milk, breast milk contains miRNAs that are potential mediators of the interactions between the host and the microbiota. Thus, we hypothesize that miRNAs from breast milk may be present in the infant's luminal content and interact with their microbiota, thereby modulating it.

Main Objective: Explore the effect of breast milk on the composition of fecal miRNAs in infants.

Primary Evaluation Criterion: Profiles and quantities of miRNAs at different time points (D10, D30, D60, M6, and M12) in the stools of exclusively breastfed infants compared to those fed with formula milk.

Secondary Objectives:

Study the effect of miRNAs from breast milk on the composition of the infant's fecal microbiota, considering environmental confounding factors, including the composition of maternal microbiota.

Investigate the effect of breast milk microbiota on the miRNA profiles present in the milk.

Study the effect of breast milk microbiota on the gut microbiota of infants. Explore the links between breast milk miRNAs, the infant's gut microbiota, and intestinal inflammation in infants.

Secondary Evaluation Criteria:

Correlations between breast milk miRNA profiles from D1 to D60 and the gut microbiota of breastfed infants from D1 to M12.

Correlations between the breast milk microbiota and the breast milk miRNA profiles from D1 to D60.

Correlations between breast milk microbiota from D1 to D60 and the infant fecal microbiota from D1 to M12.

Direct correlations between (1) breast milk miRNAs and the measurement of fecal calprotectin in infants from D1 to D60, and (2) the infant's gut microbiota and fecal calprotectin in infants from D1 to D60.

To address the research question, we plan to include 200 mother-infant dyads. Our goal is to have 30 dyads with exclusive breastfeeding for at least two months, and 30 dyads where the infant will not have received any breast milk. Each dyad will participate in the study for a period of 12 months, and the recruitment phase will last for 18 months.

At the infant's birth, we will collect stool samples from both the mother and the infant, as well as a breast milk sample from the mother.

At 10, 30, and 60 days after the infant's birth, we will request both a breast milk sample from the mother and a stool sample from the infant.

At 6 and 12 months, only a stool sample from the infant will be collected. During each visit, a clinical research coordinator will contact the mothers to gather information about both their health and diet, as well as their infant's health and diet.

Analysis of miRNAs in Breast Milk and Stool Samples: miRNAs will be extracted from infant stool samples and breast milk using next-generation Illumina sequencing (NGS). The top 10 most abundant miRNAs will then be validated through qPCR. The overall miRNA profiles will be analyzed using Principal Coordinate Analysis (PCoA).

Analysis of Gut and Breast Milk Microbiota: Stool and breast milk samples will be used for 16S rRNA gene sequencing to analyze the microbial composition. Microbiota profiles will also be examined using Principal Coordinate Analysis (PCoA).

Conditions

Breast Milk; Stools

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Breast feeding

Exclusively breastfed infants for 2 months

Stool analysis

Intervention Type: OTHER

Analysis of infant fecal microbiota

breast milk analysis

Intervention Type: OTHER

Analysis of the effect of breast milk miRNAs on infant fecal microbiota

Non breast feeding

Infants exclusively fed with formula milk

Stool analysis

Intervention Type: OTHER

Analysis of infant fecal microbiota

Interventions

Stool analysis

Analysis of infant fecal microbiota

Intervention Type: OTHER

breast milk analysis

Analysis of the effect of breast milk miRNAs on infant fecal microbiota

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Pregnant women in the 3rd trimester of pregnancy (3T) with a normal course of pregnancy up to 39 weeks consulting for the monitoring visit at the Robert-Debré hospital.
• Patients who did not receive antibiotic treatment or probiotics in 3T.
• Patient with a negative PV for Strepto B
• Patients who do not have complications such as pre-eclampsia or gestational diabetes.
• Breastfeeding (+/- milk pump) or exclusive artificial breastfeeding.
• No opposition from the mother
• Ability to master the French language required.
• Freezer at home.
• Affiliation to a social security scheme.

Exclusion Criteria

• Cesarean delivery
• Perinatal pathologies (Anoxia, IUGR, etc.)
• Neonatal pathologies (FGR, malformations, etc.)
• Initial choice of mixed breastfeeding
• Patient under AME (State Medical Aid)Critères d'exclusions :
• Antibiotics for the mother or child before day 60
• Antifungal for the mother or child before day 60
• Complete cessation of breastfeeding before day 60

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexis MOSCA, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Robert Debre Hospital Assistance Publique Hôpitaux de Paris

Paris, , France

Countries

France

Central Contacts

Alexis MOSCA, MD

Role: CONTACT

alexis.mosca@aphp.fr

0187891646

Servane ALIROL-BECHON, PhD

Role: CONTACT

servane.alirol-bechon@aphp.fr

01.87.89.16.46

Facility Contacts

Alexis MOSCA, MD

Role: primary

alexis.mosca@aphp.fr

01.87.89.16.46

Servane ALIROL-BECHON, PhD

Role: backup

servane.alirol-bechon@aphp.fr

01.87.89.16.46

Other Identifiers

IDRCB: 2024-A01059-38

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP240711

Identifier Type: -

Identifier Source: org_study_id