Aim: Human gut microbiota is an important determinant of health and disease. Discoveries from recent microbiome studies have been postulated as actionable targets to treat malnutrition, diabetes, obesity among other conditions. The role of the gut microbiome on the development of the human musculoskeletal system is yet to be established. The aim of our study was to investigate the association between bacterial operational taxonomic units (OTUs) of the gut in relation to bone mineral density levels in healthy children.
Methods: This study is embedded in the Generation R Study, a prospective multiethnic birth cohort in Rotterdam, The Netherlands. We included 2,173 children with a mean age of 9.8 (S.D.=1.0 years) with total body DXA measurements (GE-Lunar iDXA) and 16S rRNA v3-v4 microbiome profiles determined from stool samples. We assessed the association of total body (less head) BMD (TB-BMD) with OTU relative abundance (RA) using the MASSLIN approach, followed by mean comparison of TB-BMD levels between bacterial profile carriers and linear testing of OTU-RA in the children where the OTU was present. All analyses were adjusted for age, sex, BMI, genomic principal components and technical covariates, Multiple testing was accounted for using FDR <0.05.
Results: Enterococccus faecium RA was positively associated with TB-BMD (FDR=0.008), but not after correction for BMI (FDR=0.051). TB-BMD of children positive for Enterococccus faecium (n=278; 13%) was 0.25 S.D. higher (P=0.001) than that of children in which this bacteria was absent, even after adjustment for BMI (P=0.001). In children positive for Enterococccus faecium TB-BMD was 0.6S.D. higher per RA unit increase (P=0.03), though this effect was no longer significant after adjustment for BMI (P=0.2).
Conclusion: Human gut microbiota influences bone mineral density in children. Enterococccus faecium, an active component of the Lactiferm probiotic has a positive effect on BMD, however, not fully independent of BMI. Our results are in line with animal models showing that incorporation of Enterococccus faecium in the diet increases the absorption of magnesium and phosphorus exerting positive effects in bone growth and immunological resistance. Replication of these findings will allow establishing probiotics (Enterococccus faeciumI) in the diet as beneficial to bone health of children.
Disclosure: The authors declared no competing interests.