Changes in Bone Tissue Strength Caused by Disruption of the Gut Microbiome Depend on Stage of Skeletal Growth

The gut microbiome influences bone morphology and density. Recently, we demonstrated that disruption of the gut microbiome throughout life (4-16wks of age in mice) reduces the mechanical performance of whole bone at skeletal maturity by modifying bone tissue material properties. However, it is unclear if disruption of the gut microbiome alters all bone tissue or only affects bone tissue at the time of formation. To test the idea that the microbiome influence bone tissue at the time of formation, we disrupted the microbiome at different stages of growth and determined the effects on whole bone strength at skeletal maturity. Male mice (B6.129S1-Tlr5tm1Flv/J) were divided into groups (n=11-15/group, 37 total): disrupted microbiome from 4-10wks, disrupted microbiome from 10-16wks, and untreated. Whole bone strength was determined with 3-point bending to failure. Disruption of the microbiome from 4-10wks resulted in a 17.2% reduction in tissue strength as compared to untreated mice. The difference in tissue strength among groups was likely due to the amount of bone tissue formed during disruption of the microbiome. Our findings demonstrate that an impaired gut microbiome at a crucial point in skeletal growth can have a long lasting effect on bone tissue strength at skeletal maturity.