Abstract
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 (β: − 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 (β: 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.
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Data availability
The sequencing data that support the findings of this study has been made publicly available at the NIH National Center for Biotechnology Information Sequence Read Archive (SRA) with BioProject ID PRJNA640436. Supplementary information is available for this paper.
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Acknowledgements
We are grateful to the study participants. We want to thank Huanchang Yan, Yuting Hao, Yongxin Chen, Jiahua Zhang, Wenyi Guan, Ye Tong, Zhicong Zeng and Gaopei Huang for their help in sample collection.
Funding
This work was supported by the National Natural Science Foundation of China (No. 81973045) and Natural Science Foundation of Guangdong Province, China (Grant No. 2018A0303130222).
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Conception and design of the study: ZQZ and ZC. Collection of the data: FYC, YHW, DFX, JW, WKA and LJP. Analysis: FYC and YHW, QZW provided critical comments during the manuscript revision. Drafting of the paper: FYC and ZQZ. All authors read, revised, and approved the final draft.
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The present study was approved by the Ethical Review Board of Public Health at Sun Yat-sen University (201549) and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The parents or legal guardians of all participants provided written informed consent prior to enrollment.
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Chen, F., Wei, Q., Xu, D. et al. The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study. Eur J Nutr 60, 4505–4517 (2021). https://doi.org/10.1007/s00394-021-02597-x
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DOI: https://doi.org/10.1007/s00394-021-02597-x