Microbes matter: exploring the connection between infant gut microbiota and bone development

Authors: CAVINESS, PERRY - University Arkansas For Medical Sciences (UAMS); MULAKALA, BHARATH - Texas A&M University; LORENZO, OXANA - University Arkansas For Medical Sciences (UAMS); LINDEMANN, STEPHEN - Purdue University; ROSA, FERNANDA - Texas Tech University; Yeruva, Venkat; CHEN, JIN-RAN - University Arkansas For Medical Sciences (UAMS); YAO, TIANMING - Purdue University

Submitted to: Calcified Tissue International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2025
Publication Date: 7/27/2025
Citation: Caviness, P., Mulakala, B., Lorenzo, O.P., Lindemann, S.R., Rosa, F., Yeruva, V., Chen, J., Yao, T. 2025. Microbes matter: exploring the connection between infant gut microbiota and bone development. Calcified Tissue International. 116(2025). Article 90. https://doi.org/10.1007/s00223-025-01395-5.
DOI: https://doi.org/10.1007/s00223-025-01395-5

Interpretive Summary: Human milk is considered a good source of nutrition for infants and is thought to be necessary for bone and skeletal development. In infants, human milk feeding can assist in promoting the growth and development of beneficial bacteria present in the intestines known as the gut bacteria. Maternal secretor status, the ability to secrete blood group antigens in bodily fluids, is one factor in human milk that can influence the concentration and percentage of different gut bacteria. To investigate, infant gut bacteria that consumed secretor or non-secretor mothers milk or cow's milk formula, young mice were given the different gut microbiota and the effect on bone development was investigated. We found that mice given gut bacteria from milk formula fed infants showed lower bone growth and development than in control mice or mice given gut bacteria from human milk (both secretor and non-secretors mothers) fed infants. Results from this study suggest that milk formula feeding for infants may not be the optimal for optimizing bone growth and development.

Technical Abstract: Breast 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 breast milk can influence infant microbiome composition. One such factor is the type of oligosaccharide present, which is determined in part by maternal secretor status, 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 breast 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 was 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 respectfully, while 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 controls. Measurement of bone marrow plasma inflammatory factor levels shows a significant increase in TNF-a and IL-1ß for SMM and NSM mice, both potential promoters of osteoclastogenesis under certain conditions, compared to MFM and control mice. Data suggests that milk formula feeding may suppress infant bone growth and development by altering gut microbiome composition.