AUTHOR=Chen Shuai , Zhou Guowei , Han Huawei , Jin Jie , Li Zhiwei 

TITLE=Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1178831

DOI=10.3389/fendo.2023.1178831

ISSN=1664-2392

ABSTRACT=Background
Recent studies have reported that gut microbiota is essential for preventing and delaying the progression of osteoporosis. Nonetheless, the causal relationship between gut microbiota and the risk of osteoporosis has not been fully revealed.
Methods
A two-sample Mendelian randomization analysis based on a large-scale genome-wide association study was conducted to investigate the causal relationship between gut microbiota and BMD. Instrumental variables for 211 gut microbiota taxa were obtained from the available GWAS meta-analysis (n=18,340) conducted by the MiBioGen consortium. And the summary-level data for BMD were from the Genetic Factors for Osteoporosis Consortium, which involved a total of 32,735 individuals of European ancestry. The inverse-variance weighted (IVW) method was performed as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses by using multiple methods. Finally, a reverse MR analysis was applied to evaluate reverse causality.
Results
According to the IVW method, we found that 9, 6, and 8 genetically predicted gut microbiota were associated with lumbar spine (LS) BMD, forearm (FA) BMD, and femoral neck (FN) BMD, respectively. Among them, the higher genetically predicted Genus Prevotella9 level was correlated with increased LS-BMD (β = 0.125, 95% CI: 0.050–0.200, P = 0.001) and FA-BMD (β = 0.129, 95% CI: 0.007–0.251, P = 0.039). And the higher level of genetically predicted Family Prevotellaceae was associated with increased FA-BMD (β = 0.154, 95% CI: 0.020–0.288, P = 0.025) and FN-BMD (β = 0.080, 95% CI: 0.015–0.145, P = 0.016). Consistent directional effects for all analyses were observed in both the MR Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy or outliers for the causal effect of specific gut microbiota on BMD (P > 0.05). In reverse MR analysis, there was no evidence of reverse causality between LS-BMD, FA-BMD, FN-BMD and gut microbiota (P＞0.05).
Conclusion
Genetic evidence suggested a causal relationship between gut microbiota and BMD, and identified specific bacteria taxa that regulate bone mass variation. Further exploration of the potential microbiota-related mechanisms of bone metabolism might provide new approaches to the prevention and treatment of osteoporosis.