Intake of neutral core human milk oligosaccharides (HMOs) during early life improves long-term bone quality.

Infancy is a key period for bone growth, determining bone strength later in life. Studies have provided early insights into the role that human milk oligosaccharides (HMOs) may play in growth, potentially through their effects on the microbiome. However, focus was on sialylated HMOs whereas neutral core HMOs represent the most abundant class in human breast milk. We explored impact on bone quantity, quality and strength in 1year old female minipigs exposed to neutral HMOs during preweaning. Milk formula led to significant lower bone mineral density and quality compared to sow-fed (positive control). Milk formula enriched in neutral HMOs led to higher tibia bone density, structure and matrix quality compared to milk formula, leading to similar bone strength as in naturally sow-fed, whereas sialylated HMOs was not able to significantly differentiate than milk formulae. We identify a specific correlation between neutral HMOs, bone and microbiome, with the novel taxonomies Turicibacter sanguinis and Paraprevotella clara associating with HMO-mediated bone strength. This study provides important insights on the role of different HMO subtypes on bone health and possible associated adaptations in microbiome taxa, providing perspectives for new nutritional solutions for bone growth in early life.