Journal of bone and mineral metabolism · 2026
Causal association between gut microbiota and osteonecrosis in European populations: a two-sample Mendelian randomization analysis.
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Li Haiqing, Yang Zhen, Li Mingfeng, Yang Huiqin, Liu Dejiu, Bi Yuke, Dai Xuejun, Chen Xin, Miao Lirong, Yang Fang, Chen Zhuoyuan
Аннотация
INTRODUCTION: Recent studies have linked gut microbiota composition to osteonecrosis, but the causal relationship remains unclear. Clarifying this relationship is clinically important because osteonecrosis currently lacks early biomarkers and etiology-targeted therapies; if causal, the gut microbiome would offer a readily modifiable intervention target.
METHODS: We conducted a two-sample Mendelian randomization analysis to explore this relationship. Exposure data were sourced from the MiBioGen consortium (N = 18,340), while outcome data on osteonecrosis were obtained from FinnGen (N = 392,580). The Inverse Variance Weighted method was used as the primary analytical approach, supplemented by comprehensive sensitivity analyses to assess the robustness of our findings.
RESULTS: Our analysis screened 196 microbial taxa and identified seven taxa associated with osteonecrosis risk in European populations. Protective effects were noted for the genus Odoribacter (OR = 0.579; P = 0.027) and family Alcaligenaceae (OR = 0.703; P = 0.049). Conversely, increased risk was linked to the genus Eubacterium fissicatena group (OR = 1.272; P = 0.046), genus Bifidobacterium (OR = 1.372; P = 0.038), order Bifidobacteriales (OR = 1.412; P = 0.023), family Bifidobacteriaceae (OR = 1.412; P = 0.023) and phylum Actinobacteria (OR = 1.750; P = 0.001). Sensitivity analyses confirmed the robustness of these findings, with no evidence of pleiotropy or heterogeneity.
CONCLUSION: This study establishes a causal link between gut microbiota composition and osteonecrosis, suggesting that gut microbiota may be a modifiable factor in its pathogenesis. Further research is needed to elucidate underlying mechanisms and evaluate microbiota-targeted interventions for prevention and treatment.
METHODS: We conducted a two-sample Mendelian randomization analysis to explore this relationship. Exposure data were sourced from the MiBioGen consortium (N = 18,340), while outcome data on osteonecrosis were obtained from FinnGen (N = 392,580). The Inverse Variance Weighted method was used as the primary analytical approach, supplemented by comprehensive sensitivity analyses to assess the robustness of our findings.
RESULTS: Our analysis screened 196 microbial taxa and identified seven taxa associated with osteonecrosis risk in European populations. Protective effects were noted for the genus Odoribacter (OR = 0.579; P = 0.027) and family Alcaligenaceae (OR = 0.703; P = 0.049). Conversely, increased risk was linked to the genus Eubacterium fissicatena group (OR = 1.272; P = 0.046), genus Bifidobacterium (OR = 1.372; P = 0.038), order Bifidobacteriales (OR = 1.412; P = 0.023), family Bifidobacteriaceae (OR = 1.412; P = 0.023) and phylum Actinobacteria (OR = 1.750; P = 0.001). Sensitivity analyses confirmed the robustness of these findings, with no evidence of pleiotropy or heterogeneity.
CONCLUSION: This study establishes a causal link between gut microbiota composition and osteonecrosis, suggesting that gut microbiota may be a modifiable factor in its pathogenesis. Further research is needed to elucidate underlying mechanisms and evaluate microbiota-targeted interventions for prevention and treatment.