Microbes Matter: Exploring the Connection Between Infant Gut Microbiota and Bone Development

Human milk, compared to milk formula, is considered the optimal source of nutrition for infants as it can shape offspring microbiome composition, which is necessary for the production of key biomolecules that aid in development of infant physiological systems. A variety of factors in human milk can influence infant microbiome composition. One such factor is the type of oligosaccharides present, which is determined in part by maternal secretor status and itself determined by expression of fucosyltransferase-2 (FUT2). The aim of this study was to investigate the effects of secretor or non-secretor human milk as well as infant milk formula on infant gut microbiome composition and whether these changes in microbiota impact bone development. Fecal microbiota transfer from infants fed human milk from secretor mothers (SMM) or non-secretor mothers (NSM) as well as those fed infant milk formula (MFM) into 21-day-old germ-free mice were performed. After 35 days, gut microbiome composition and bone development were analyzed using 16S rRNA sequencing and µCT analysis. At the genus level, Phocaeicola and Akkermansia are upregulated for SMM and NSM mice respectively, while family Ruminococcaceae is increased for MFM mice. Percent bone volume (BV/TV) and trabecular number (Tb N) were significantly decreased for MFM mice but unaltered for SMM and NSM mice compared to germ-free controls (GF CTRL). Measurement of bone marrow plasma inflammatory factor levels shows a significant increase in TNF-α and IL-1β for SMM and NSM mice, both potential promoters of osteoclastogenesis under certain conditions, compared to MFM and GF CTRL mice. Data suggests that milk formula feeding may suppress infant bone growth and development by altering gut microbiome composition.