Identifying microbial signatures for patients with postmenopausal osteoporosis using gut microbiota analyses and feature selection approaches

Huang, Dageng; Wang, Jihan; Zeng, Yuhong; Li, Qingmei; Wang, Yangyang

doi:10.3389/fmicb.2023.1113174

Cited by 7 publications

(1 citation statement)

References 55 publications

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“…Our findings show that the results of the association between BMD and gut microbiota differ in different skeletal sites. A previous study found that gut microbiota composition had a higher correlation with BMD values/T scores in the hip than in the lumbar spine (Huang et al, 2023). Only pelvic BMD was eventually found to have modest associations with gut microbiota in another Polygenic Risk Score (PRS) analysis, which was performed using 31 different sites of BMD as the outcome (Cheng et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the relationship between gut microbiota and bone mineral density: a two-sample Mendelian randomization study

Xue,

Wang,

Liu

et al. 2024

Front. Microbiol.

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BackgroundEmerging evidence from observational studies and clinical trials suggests a connection between the gut microbiota and variations in bone mineral density (BMD). Nonetheless, the specific association between gut microbiota and BMD alterations at different skeletal sites has not been comprehensively explored. To address this, we employed Genome-Wide Association Study (GWAS) summary statistics from a publicly accessible database, conducting a two-sample Mendelian Randomization analysis to elucidate the potential causal relationship between gut microbiota composition and BMD.MethodsThis study utilized two distinct thresholds for screening instrumental variables (IVs), followed by an extensive series of quality control procedures to identify IVs that were significantly related to exposure. Gut microbiota were classified into two sets based on hierarchical levels: phylum, class, order, family, and genus. Bone mineral density (BMD) data were systematically collected from four skeletal sites: femoral neck, lumbar spine, forearm, and heel. For Mendelian Randomization (MR) analysis, robust methods including Inverse-Variance Weighting (IVW) and the Wald Ratio Test were employed. Additional analytical tests such as the Outlier Test, Heterogeneity Test, ‘Leave-One-Out’ Test, and Pleiotropy Test were conducted to assess the impact of horizontal pleiotropy, heterogeneities, and the genetic variation stability of gut microbiota on BMD causal associations. The MR Steiger Directionality Test was applied to exclude studies with potential directional biases.ResultsIn this two-sample Mendelian randomization analysis, we utilized five sets of exposure GWAS (Genome-Wide Association Studies) summary statistics and four sets of outcome GWAS summary statistics. The initial analysis, applying a threshold of p < 5 × 10−6, identified 48 significant causal relationships between genetic liability in the gut microbiome and bone mineral density (BMD). A subsequent analysis with a more stringent threshold of p < 5 × 10−8 uncovered 14 additional causal relationships. Upon applying the Bonferroni correction, 9 results from the first analysis and 10 from the second remained statistically significant.ConclusionOur MR analysis revealed a causal relationship between gut microbiota and bone mineral density at all sites, which could lead to discoveries in future mechanistic and clinical studies of microbiota-associated osteoporosis.

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Section: Discussionmentioning

confidence: 99%