Research Paper Volume 12, Issue 11 pp 10736—10753

Structural and functional changes of gut microbiota in ovariectomized rats and their correlations with altered bone mass

Sicong Ma1, , Jinhong Qin2, , Yongqiang Hao1, , Ying Shi3, , Lingjie Fu1, ,

  • 1 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2 Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 3 Department of Orthopaedics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

Received: December 12, 2019       Accepted: April 27, 2020       Published: June 2, 2020
How to Cite

Copyright © 2020 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


As a critical factor involved in the maintenance of physiological homeostasis, the gut microbiota (GM) reportedly plays a key role in bone development. To date, the association between the GM and steroid deficiency-induced osteoporosis remains poorly understood. Forty female Sprague Dawley rats were divided into an ovariectomy (OVX) or control group. We performed 16S rRNA and metagenome sequencing, to compare diversity, taxonomic differences, and functional genes. The GM composition did not change in the control group and the number of operational taxonomic units increased significantly following ovariectomy. Alpha diversity, determined by ACE estimator, CHAO estimator, the Shannon index, and the Simpson index showed an increasing trend after ovariectomy. Samples in the OVX group were well clustered both pre- and post-ovariectomy, as demonstrated by principal coordinate 1 (PC1) and PC2. Functional genes of GM, including those involved in synthesis and metabolism of carbohydrates and nucleotides, microbial structure, and heme, as well as hemin uptake and utilization, increased at the early stage of osteoporosis. We observed that Ruminococcus flavefaciens exhibited the greatest variation in abundance among the GM and this was also associated with osteoclastic indicators and the estrobolome. Specific changes in fecal microbiota are associated with the pathogenesis of steroid deficiency-induced osteoporosis.


BMD: Bone mineral density; CON: Control; CTX: I collagen carboxy-terminal peptide; F/B ratio: Firmicutes/Bacteroidetes ratio; FOS: Fructooligosaccharides; GF: Germ free; GM: Gut microbiota; LPS: Lipopolysaccharide; MAMPs: Microbe associated molecular patterns; MDP: Muramyl dipeptide; OTUs: Operational taxonomic units; OVX: Ovariectomy; PC: Principal coordinate; PCoA: Principal coordinate analysis; P1NP: Procollagen type 1 N-terminal propeptide; RA: Rheumatoid arthritis; RDA: Redundancy analysis; SCFAs: Short chain fatty acids; TLRs: Toll-like receptors; VEGF: Vascular endothelial growth factor; VOI: Volume of interest.