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

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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).

Author information

Author notes

  1. Fengyan Chen, Qinzhi Wei have equally contributed to this work.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Nutrition and Food Hygiene, School of Public Health, Southern Medical University, Guangzhou, China

    Fengyan Chen, Dafeng Xu, Yuanhuan Wei, Jue Wang, William Kwame Amakye & Zheqing Zhang

  2. Guangdong Provincial Key Laboratory of Tropical Disease Research, Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, China

    Qinzhi Wei

  3. Department of Nutrition, Chenzhou First People’s Hospital, Chenzhou, China

    Dafeng Xu

  4. Department of Clinical Nutrition, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China

    Yuanhuan Wei

  5. Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Hygiene Detection Center, School of Public Health, Southern Medical University, Guangzhou, China

    Jialiang Pan

  6. Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Zhuang Cui

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  1. Fengyan Chen
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Contributions

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.

Corresponding authors

Correspondence to Zhuang Cui or Zheqing Zhang.

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Conflict of interest

The authors declare no conflict of interest.

Ethical standards

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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