Human Milk Oligosaccharides' Impact on Maturation of the Gut Microbiota

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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.

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