Plenary Poster ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Aims: The gut microbiome is associated with bone health in animals and adult humans, but longitudinal evidence in childhood is lacking(1). We aim to investigate the association between the gut microbiome and subsequent bone health in childhood.

Methods: We used data from the COPSAC₂₀₁₀ study, an ongoing population-based mother-child cohort study in Denmark. Infant gut microbiome was measured at 1-week (n=445), 1-month (n=492), 1(n=509), 4(n=350), and 6-years (n=327) by 16S rRNA sequencing (V4 region). Total body less head (TBLH) bone mineral density (BMD) and area-adjusted bone mineral content (aBMC) were measured by dual-energy x-ray absorptiometry (DXA) at age six. The associations between gut microbiome characteristics, including α-diversity (within sample) and relative abundance, were assessed using multiple linear regression and β-diversity (between sample) by PERMANOVA. Differential abundance was assessed by LIMMA-ALR after stratifying bone outcomes into tertiles.

Results: Overall, the study did not reveal consistent associations between the early-life gut microbiome and bone health at 6 years. However, in 1-year-olds, increase in α-diversity was associated with decrease in BMD, and in 4-year-olds, with decrease in BMD and aBMC (Table). β-diversity at 6-years was associated with concurrent BMD. No associations with α/β-diversity were observed for other ages. After correction for multiple testing, abundance of Sutterella at 1-year was negatively associated with later aBMC. No other taxa at any age were significantly associated with bone health outcomes at six. Compared to the low tertile, high BMD had lower Escherichia-Shigella abundance (LogFC=-1.65;p.adj=0.038) at 1-month. At age four, Sporobacter (LogFC=-1.40;p.adj<0.001), Christensenellaceae R-7 group (LogFC=-1.33;p.adj=0.028), and Oscillibacter (LogFC=-1.04;p.adj=0.028) were found in lower abundances in children with medium aBMC. There were no differentially abundant taxa at other ages.

Conclusion: While we observed some associations, our study does not suggest the early life gut microbiome to be a major contributor to bone health at six.