Human Milk Oligosaccharides' Impact on Maturation of the Gut Microbiota

NCT07026526 | Completed

• 2 other identifiers: Milkomecohort2025RP2 grant/1026-00386B
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Human milk oligosaccharides (HMOs) are the third largest component of human milk after fat and milk sugar (lactose). HMOs play an important role in selecting the gut microbiota (GM) in newborn breastfed infants. However, the mechanisms underpinning the maturation process that the gut microbiota undergoes during the transition from a breast milk to a solid food diet (weaning) and the impact of HMOs on this transition remain unknown. The aim of the present study:

• Evaluate the contribution of HMOs to the maturation of the GM during weaning
• Analyze the utilization of HMOs and other complex carbohydrates from diet and from the human host by the GM during the weaning period We have recruited a cohort of healthy volunteer mothers and their infants (n=9 pairs, two were disqualified and 7 pairs were included in the final analyses). After oral and written informed consent, we collected stool samples from the mother-infant dyads at three time points: 1) just before the introduction of solid food (weaning start), 2) At a time point corresponding to 70% of the infant's meals being breast milk and 30% being toddler food within a 24-hour period (early weaning), and 3) late weaning, defined as the time point corresponding to approx. 30% and 70% of an infant's meals are breast milk and solid food, respectively, within a 24-hour period (late weaning). The samples have been collected and stored in a Pseudoanonymous Research Bank at the Technical University of Denmark until the data have been analyzed and published, except for participants who allow storage indefinitely through a separate written consent form. In this case, excess material left over after the experiment will be transferred to a Pseudoanonymous Biobank for future research. The stool samples have been analyzed for gut microbiota composition and carbohydrate utilization potential (based on whole metagenome sequencing). The fecal samples were also enriched on different carbohydrate sources and the enriched consortia were sequenced and analyzed as above. Strains were also isolated from both mother and infant samples via growth on a variety of carbohydrate sources. The genome analyses were performed exclusively on bacteria and human DNA was excluded. In addition, selected fecal samples were used to colonize germfree mice and the mice were fed with alternating customized mother's milk-like and dietary fiber-rich diets. Similar metagenome analyses were performed on selected fecal samples from this mouse intervention study.

Conditions

Study Focus: Weaning Gut Microbiota

Keywords

Early life gut microbiome; Human milk oligosaccharides; mother's milk; weaning

Outcome Measures

Primary Outcomes (1)

• Contribution of HMOs to the weaning gut microbiome maturation

  Evaluating utilization of HMOs by the gut microbiota during weaning is expected to inform the importance of HMOs in the selection and the fitness of specific gut bacteria that expand or colonize the infant gut during the different weaning stages.

  From enrollment until late weaning (3-7 month)

Study Arms (1)

Mother-infant dyad

The gut microbiome of the cohort, consisting of mother-infant dyads will be analyzed.

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: For mothers the gender is predefined, whereas for infants there are no gender restriction.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Residents of the greater Copenhagen area, Denmark.

You may qualify if:

• \. Mothers
• Age 18 years or older
• Non-smoker
• Residents of the greater Copenhagen area
• Danish or English speaking
• No history of gestational diabetes during pregnancy (received standard care from midwife)
• Pre-pregnancy body mass index between 20-30 kg/m2
• Categorised as low risk pregnancy
• Had a vaginal full-term delivery (gestational age ≥37 weeks)
• Planned to exclusively breastfeed until non-breast milk diet (solid food) introduction
• For infants:
• \- No additional criteria than what is specified above for the mother

You may not qualify if:

• Mother Use of antibiotics after the 6th month of the last pregnancy
• Infant
• Admission to the neonatal or intensive care unit
• Use of antibiotic since birth or thereafter
• Infant formula feeding during the study

Sponsors & Collaborators

• Technical University of Denmark: lead
• Copenhagen University Hospital at Herlev: collaborator

Study Sites (1)

Department of Neonatal and Pediatric Intensive Care Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Fecal samples, which will only be retained if subjects have consented to use the material for future research.

Study Design

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

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: August 17, 2022
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: June 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)