Gut Microbiome in early life and Bone Health Outcomes at Age 6: a Danish Mother-Child Cohort Study.

The gut microbiome is associated with bone mass acquisition, yet evidence in childhood remains limited. Given that lower peak bone mass predicts osteoporosis in later life, understanding early influences is important. This analysis explores the association between the early life gut microbiome and bone health in later childhood. Data was obtained from 700 children recruited in pregnancy and followed prospectively within the Copenhagen Prospective Studies on Asthma in Childhood2010 cohort, a population-based mother-child cohort. The infant gut microbiome was measured at 1 wk (n = 445), 1 mo (n = 492), 1 yr (n = 508), 4 yr (n = 350), and 6 yr (n = 327) of age by 16S ribosomal ribonucleic acid amplicon sequencing targeting the fourth variable region. Total body less head bone mineral density and area-adjusted bone mineral content were measured by dual-energy X-ray absorptiometry at 6 yr of age. Associations were investigated by multiple linear regression, permutational analysis of variance, differential abundance analysis, and Random Forest machine learning. There were few associations between the early-life gut microbiome and bone health outcomes at age six. We found negative associations between alpha (within-sample) diversity and area-adjusted bone mineral content at 4 yr. Beta (between-sample) diversity of the gut microbiome at 6 yr was associated with concurrent bone mineral density. Escherichia-Shigella abundance at 1 mo of age associated with lower bone mineral density. Sutterella abundance at 1 yr was associated with lower bone mineral density and area-adjusted bone mineral content at 6 yr. There were no other associations between the gut microbiome and bone outcome measures at any time point. In a well-powered unselected cohort study with longitudinal sampling of the gut microbiome, there were some suggestive but no consistent associations between the early gut microbiome and bone health outcomes at 6 yr of age.