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. 2024 May 31:15:1419566.
doi: 10.3389/fendo.2024.1419566. eCollection 2024.

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

Hefang Xiao #  1   2   3 , Yaobin Wang #  1   2   3 , Yi Chen #  1   2   3 , Rongjin Chen  1   2   3 , Chenhui Yang  1   2   3 , Bin Geng  1   2   3 , Yayi Xia  1   2   3
Affiliations

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

Hefang Xiao et al. Front Endocrinol (Lausanne). .

Abstract

Background: Postmenopausal 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.

Methods: We 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.

Results: The 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.

Conclusion: This 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.

Keywords: GWAS; Mendelian randomization; gut microbiota; gut-bone axis; osteoclasts; postmenopausal osteoporosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Workflow of our research.
Figure 2
Figure 2
Mendelian analysis results for gut microbiota and osteoclasts; (A): IVW heatmap results of the causal relationship between gut microbiota and osteoclasts; (B): Forest plot results showing the association between gut microbiota and osteoclasts.
Figure 3
Figure 3
Mendelian analysis results for gut microbiota and postmenopausal osteoporosis; (A): IVW heatmap results of the causal relationship between gut microbiota and postmenopausal osteoporosis; (B): Forest plot results showing the association between gut microbiota and postmenopausal osteoporosis.
Figure 4
Figure 4
Selection and Mendelian analysis of key genes. (A): Venn diagram intersecting key microbiota for osteoclasts and key microbiota for postmenopausal osteoporosis; (B): Forest plot showing the validation of key genes based on eQTL data.
Figure 5
Figure 5
Single-cell data analysis results; (A): Cell distribution map after clustering annotation of the dataset; (B): Bubble chart showing the proportion of key genes across different cells.
See this image and copyright information in PMC

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