The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study.

PURPOSE: We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9 years. METHODS: In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD) and bone mineral content (BMC) for total body (TB) and total body less head (TBLH). Z score of TBLH BMD was calculated based on the recommended reference. RESULTS: Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium and Blautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (ß: - 0.207 to - 0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (ß: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively. CONCLUSIONS: The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.