Frontiers in Endocrinology (May 2024)

Gut-bone axis research: unveiling the impact of gut microbiota on postmenopausal osteoporosis and osteoclasts through Mendelian randomization

  • Hefang Xiao,
  • Hefang Xiao,
  • Hefang Xiao,
  • Yaobin Wang,
  • Yaobin Wang,
  • Yaobin Wang,
  • Yi Chen,
  • Yi Chen,
  • Yi Chen,
  • Rongjin Chen,
  • Rongjin Chen,
  • Rongjin Chen,
  • Chenhui Yang,
  • Chenhui Yang,
  • Chenhui Yang,
  • Bin Geng,
  • Bin Geng,
  • Bin Geng,
  • Yayi Xia,
  • Yayi Xia,
  • Yayi Xia

DOI
https://doi.org/10.3389/fendo.2024.1419566
Journal volume & issue
Vol. 15

Abstract

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BackgroundPostmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention.MethodsWe employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287.ResultsThe outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis.ConclusionThis study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.

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